tbuckley/cabot-search huggingface dataset:
NIMG-58. USEFULNESS OF HISTOGRAM ANALYSIS IN RING-ENHANCING INTRACRANIAL LESIONS
Authors: Manish Kolakshyapati, Fumiyuki Yamasaki, Akira Hashizume, Takeshi Takayasu, Motoki Takano, Vega Karlowee, Yuji Akiyama, Kaoru Kurisu
Journal: Neuro-Oncology (2017)

Several intracranial pathologies present as ring-enhancing lesion in conventional MR images. These include glioma, brain metastases, lymphoma, brain abscess and demyelinating disorders. Based on conventional MR images alone, it is sometimes difficult to distinguish them visually. The purpose of this study is to employ simple technique of histogram analysis of MRI for differentiating them. Preoperative MR images including T2WI and post-contrast T1WI were analyzed retrospectively after receiving approval from institutional review board. 18 patients of histologically confirmed brain abscess, 64 glioblastoma, 32 malignant lymphoma, 46 brain metastases (METS) and 16 multiple sclerosis (MS) were included. T2WI and post-contrast T1WI were overlapped and histogram analysis was performed using an image fusion software programmed in Matlab at our institute. Presence and location of differential peaks of T2WI and post-contrast T1WI were assessed visually. Statistical analysis of the location of the differential peaks was performed. The histogram study revealed 4 different patterns. The first pattern showed no differential T2 hypointensity peak within the contrast enhanced margins. The second pattern had T2 hypointensity peak inside the enhanced margin with a sharp peak. The third pattern consisted of the differential peaks of T2 hypointensity overlapping the enhanced margin and the fourth had T2 hypointensity peak immediately external to the ring. Pattern 1 was specific for MS (93.3%) while pattern 4 was specific for GBM (38.8%). Pattern 2 was found in 50% of brain abscess and 24% of METS. Pattern 3 was seen in 41% of METS and 18.7% of brain abscess. Presence of differential peaks of T2 hypointensity in histogram inside contrast enhanced margin is mostly seen in brain abscess. MS shows a characteristic pattern in histogram analysis. Some glioma also show a specific pattern in histogram analysis. Histogram analysis is a simple and efficient technique to differentiate these pathologies visually.
CBIO-20. miR-4516 IS A NOVEL PROGNOSTIC MARKER AND PROMOTES PROLIFERATION AND INVASION IN GLIOBLASTOMA
Authors: Tiantian Cui, Erica H Bell, Joseph P McElroy, Marjolein Geurts, Pooja Manchanda Gulati, Aline Paixao Becker, Jessica Fleming, Linlin Yang, Ziyan Liu, Ashley Gray, Pierre Robe, Arnab Chakravarti
Journal: Neuro-Oncology (2017)

Glioblastomas (GBMs) are the most aggressive high-grade brain tumor, with average survival of less than 15 months. Although the mechanisms of tumorigenesis are still being elucidated, microRNAs (miRNAs) have become promising candidates as novel prognostic biomarkers in GBM. This study aimed to assess the prognostic value of miR-4516 in GBM patients and investigate its oncogenic role in GBM as well as the underlying cellular and molecular mechanisms. Total RNA was isolated from 268 formalin-fixed, paraffin-embedded patient tissue blocks. miRNAs were assayed simultaneously using the nCounter human miRNA v3a assay (NanoString Technologies; Seattle,WA). Functional characterization studies were conducted in vitro by cell proliferation and trans-well invasion assays. The downstream targets of miR-4516 were determined using qPCR, immunoblotting, and a dual luciferase reporter assay. Human tumor xenografts were generated to explore the role of miR-4516 in GBM tumorigenesis in a mouse model. Our results demonstrated that high expression of miR-4516 correlated with poor prognosis in GBM patients [HR=1.5, 95% CI (1.2–2.0), p=0.002]. Overexpression of miR-4516 dramatically enhanced cell proliferation both in vitro and in xenograft tumor models, and promoted GBM cell invasion. While conducting a downstream targeting study, we found that miR-4516 tumor-promoting effects were mediated in part via direct targeting of PTPN14 (protein tyrosine phosphatase, non-receptor type 14), a tumor suppressor in various cancer types. This study suggests that miR-4516 acts as a novel prognostic biomarker for GBM patients and functions as an oncogene by suppressing PTPN14 in GBM suggesting miR-4516 may serve as a future therapeutic target in GBM.
IMMU-30. TCR Vb CLONAL EXPANSION PREDICTS RESPONSE TO ADOPTIVE IMMUNOTHERAPY AGAINST MEDULLOBLASTOMA
Authors: Catherine Flores, Tyler Wildes, Christina Pham, Rebecca Abraham, Ginger Mooree, Duane Mitchell
Journal: Neuro-Oncology (2017)

Adoptive cell therapy has led to robust overall response rates in patients with metastatic disease. In patients with durable responses after adoptive immunotherapy, sequencing of TCR Vβ demonstrated multiple T cell clonotypes in the adoptively transferred cells, but showed clonotypic expansion of only a select few over time and these clones persisted in peripheral blood for one or more months after transfer. The identification of antigens associated with brain tumor rejection mediated by adoptive cell therapy remains challenging given the diversity of the bulk lymphocyte populations. We have previously demonstrated that adoptive cell therapy employing ex vivo activated tumor-specific T cells using tumor-RNA pulsed dendritic cells (TTRNA-T cells) is highly efficacious against preclinical models of brain tumors refractory to radiation and chemotherapy. Without prior knowledge of the tumor antigen targeted in our adoptive cell therapy platform, we developed a novel method to identify tumor-specific T lymphocytes from the bulk of ex vivo activated TTRNA-T cells by evaluating the TCR Vβ repertoire using flow cytometry based spectratyping. In this study we demonstrate that TCR Vβ expression can be used to both identify and enrich for the tumor-specific T cells from a bulk population. In a murine model of Group 3 medulloblastoma (referred to as NSC) treated with adoptive cell therapy, TCR Vβ spectratyping revealed expansion of TCR Vβ families 5.1/5.2, 6, 8.1/8.2, and 13 in responders to therapy. Functionality assays demonstrate that these TCR Vβ families are responsible for anti-tumor reactivity against NSC medulloblastoma cells. Survival and responsiveness to immunotherapy is strongly associated with expansion of TTRNA-T cells that express TCR Vβ 8.1/8.2. These findings were corroborated in a patient with recurrent medulloblastoma who received adoptive cell therapy using autologous TTRNA-T cells. Clonal expansion of adoptively transferred tumor-reactive T cells was revealed using TCR sequencing.
P1.06-022 Prognostic Value of NLR in Overall Survival of Patients with Advanced Lung Cancer
Authors: C. Flores, A. Aguilar, L.A. Mas Lopez, J.M. Gutierrez Castañeda, R. Ruiz Mendoza, L. Pinillos-Ashton, C. Vallejos
Journal: Journal of Thoracic Oncology (2017)
CMET-19. THE ROLE OF BRAIN SPECIFIC FATTY ACID BINDING PROTEIN 7 IN BREAST CANCER METASTASES TO THE BRAIN
Authors: Alex Cordero, Deepak Kanojia, Wojciech K Panek, Annie Xiao, Meijing Wu, Atique Ahmed, Maciej S Lesniak
Journal: Neuro-Oncology (2017)

HER2 overexpression in breast cancer increases the incidence of brain metastasis. Brain metastases are established after extravasation of cancer cells in the glia followed by invasion in the brain microenvironment. To identify critical genes for establishment of brain metastases, we conducted an In silico screening of publicly available datasets. Our screening identified FABP7 to be significantly overexpressed in brain metastatic patients as compared to patients with systemic metastases. In the NKI dataset overexpression of FABP7 was also correlated with poor prognosis. FABP7 is a brain-specific gene responsible for brain development and lipid metabolism. To establish the role of FABP7 in the brain metastatic process, FABP7 shRNA knockdown studies were conducted in BT-474BrM3 cells. Our results demonstrated a reduction in invasion ability of FABP7 knockdown cells. This result was accompanied with a significant decreased expression of genes that play a key role in the metastatic process such as OCT4, NANOG, ZEB2 or Carbonic anhydrase IX (Ca9). Moreover, phosphorylation of the p38 MAPK and ATF-2, another key signaling pathway regulating metastasis, was abrogated by FABP7 knockdown, suggesting that FABP7 is required for the kinase activity of p38 MAPK. In lieu of the fact that brain is normally under hypoxic environment, we simulated hypoxia in cell culture models. Interestingly under hypoxic conditions, FABP7 knockdown cells failed to induce angiogenic and invasive markers, such as VEGFA or PTPRZ1. Altogether, our results indicate that the expression of FABP7 by brain metastatic breast cancer cells allows the breast cancer cells to invade within the central nervous system.
RBIO-02. CALPASTATIN PHOSPHORYLATION REGULATES RADIATION RESPONSE IN GLIOBLASTOMA
Authors: Emily Bassett, Kamalakannan Palanichamy, Mitchell Pearson, S Jaharul Haque, Arnab Chakravarti
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is an aggressive, malignant brain tumor that often develops resistance to conventional chemotherapy and radiation treatments. In order to identify signaling pathways involved in the development of radiation resistance, we performed mass spectrometry-based phospho-proteomic profiling of 5 GBM cell lines and normal human astrocytes before and after radiation treatment. Fold changes in phosphorylation were calculated for each peptide across all cell lines at 30 seconds and 4 hours post-radiation. We found that radiation induces phosphorylation of calpastatin, an endogenous inhibitor of calpain proteases, specifically in GBM stem cells (GSCs). Radiation-induced phosphorylation of calpastatin at a serine within the inhibitory domain was validated by western blot with a phospho-specific antibody. In order to test the functional significance of phosphorylated calpastatin, we utilized site-directed mutagenesis to generate non-phosphorylatable and phospho-mimetic calpastatin mutants. Western blot analyses of GBM cell lines stably expressing the calpastatin mutant proteins show that calpastatin phosphorylation leads to increased calpain activity following radiation treatment. Our results indicate that calpastatin phosphorylation promotes radiation resistance in GBM by increasing the activity of calpain proteases, which are known to promote survival and invasion in cancers.
TMOD-28. INTERLEUKIN-13 TARGETED PSEUDOMONAS TOXIN TREATMENT OF MALIGNANT PERIPHERAL NERVE SHEATH TUMORS
Authors: Oliver Mrowczynski, Russell Payne, Christine Mau, Alexandre Bourcier, A B Madhankumar, Becky Slagle-Webb, Kimberly Harbaugh, Elias Rizk, James Connor
Journal: Neuro-Oncology (2017)

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from peripheral nerves. A target of MPNSTs is the receptor for interleukin-13 (IL-13R). IL-13R has an α1 and α2 subtype, and activation of α1 leads to caspase-3 mediated apoptosis. MPNSTs have increased expression of the α2 subtype, IL-13Rα2. IL-13Rα2 is an oncogene that acts as a decoy receptor which has a higher affinity for IL-13, allowing cancer to evade death by binding and sequestering all of the IL-13 thus inhibiting α1 activation. Decreased α1 activation enhances tumor cell survival and augments the high potential for metastasis. The subsequent increased tumorigenicity is then followed by the devastating prognosis with five year survival ranging from a dismal 15-60%. MPNSTs are currently treated with surgical resection, sometimes requiring complete limb amputation, as well as chemoradiation, all of which demonstrate limited effectiveness, and highlight the necessity for novel therapies. The goal of this study was to demonstrate the effectiveness of intratumoral Interleukin-13 targeted pseudomonas exotoxin (IL13E13K-PE4E) for MPNST treatment. The upregulated IL-13Rα2 on MPNSTs provides a unique opportunity for utilizing IL13E13K-PE4E to precisely target MPNSTs and cause tumor cell death. We demonstrate that IL13E13K-PE4E treatment led to a 4-fold decrease in tumor progression in vivo. IHC analysis showed increased necrosis, decreased Ki67, and increased cleaved caspase-3, corroborating the in vivo findings. The specific targeting of IL-13Rα2 also leads to a decreased side effect profile due to minimal IL-13Rα2 expression in normal tissues. The current MPNST treatment paradigm is composed of 3-prongs: surgery, chemotherapy, and radiation, all of which have been demonstrated to be unsatisfactory. This study lays the groundwork for the change of this paradigm and subsequently optimal patient outcomes by the addition of a 4th prong, intratumoral treatment with IL13E13K-PE4E.
IMMU-14. TARGETING CD200 ACTIVATION RECEPTORS TO OVERCOME THE IMMUNOSUPPRESSIVE TUMOR MICROENVIRONMENT
Authors: Elisabet Ampudia-Mesias, Christopher Moertel, Elizabeth Pluhar, Michael Olin
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme is an incurable primary brain tumor. The current standard of care consists of resection followed by radiation and chemotherapy; associated with a median overall survival of 14.6 months. To overcome this dismal outcome, clinicians are turning to immunotherapeutic approaches, which have demonstrated promising results in non-CNS tumors. Recently, the FDA approved immune checkpoint inhibitor therapy for solid tumors that is otherwise refractory to standard therapy. Immune checkpoint inhibitor therapy has increased patient survival, heralding a new era for effective cancer treatment. We have recently reported that targeting an alternative immune checkpoint, CD200, inhibits tumor-induced immunosuppression without toxic side effects. We are targeting the CD200 checkpoint, which uses paired receptors (inhibitory and activation receptors) to maintain homeostasis. We demonstrated that targeting the activation receptors (CD200AR) surmounts the CD200-induced inhibitory signals, priming a potent anti-tumor response. Although the suppressive mechanism between the CD200 protein and the inhibitory receptor has been well characterized, little is known involving the CD200 activation receptors. In its native state, CD200 only binds to its inhibitory receptor, CD200R1; however, we identified multiple metalloprotease (MMP) cleavage sites within the CD200 protein. We hypothesize that MMP cleavage releases protein fragments and alters CD200 folding, exposing binding sites for the CD200AR. We developed peptide ligands to target the CD200ARs, designated as CD200AR-L. In our murine model, we reported enhanced T-cell responses with the use of the murine CD200AR-L’s. In contrast, similarly treated cells with the CD200 activation receptors knocked out or wildtype cells pulsed with a scrambled CD200AR-L failed to respond. IMPACT: Our research is highly innovative in that it uniquely focuses on a novel mechanism that tumors exploit to escape immune surveillance. The ultimate objective of this research is to understand the underlying mechanism of the CD200 blockade for effective implementation of immunotherapy against CNS tumors.
Baseline absolute neutrophil count (ANC), derived neutrophil-to-lymphocyte ratio (dNLR) and platelet-to-lymphocyte ratio (PLR) and outcome in non small cell lung cancer (NSCLC) treated with nivolumab or docetaxel: a preliminary analysis
Authors: A. Russo, A. Scimone, M. Picciotto, G. Toscano, F. Raiti, S. Sava, A. Battaglia, V. Adamo
Journal: Annals of Oncology (2017)
Coronary-Artery Aneurysm in Tocilizumab-Treated Children with Kawasaki’s Disease
Authors: Tomo Nozawa, Tomoyuki Imagawa, Shuichi Ito
Journal: New England Journal of Medicine (2017)

Coronary-Artery Aneurysm in Tocilizumab-Treated Children with Kawasaki's DiseaseTo the Editor: Kawasaki's disease is the most common systemic vasculitis in children.Coronaryartery aneurysms may develop in 25% of untreated patients.Intravenous immune globulin (IVIG), the cornerstone of therapy, can reduce the risk of coronary-artery aneurysms to 4%.However, among the therapies tested so far that have been found to be effective against IVIG-resistant Kawasaki's disease, the best choice remains a subject of controversy.Kawasaki's disease is characterized by a cytokine storm, with elevated levels of tumor necrosis factor (TNF) α, interleukin-6, granulocyte colony-stimulating factor, interleukin-1β, and interleukin-17. 1 In a trial involving children with Kawasaki's disease, infliximab, an anti-TNF-α antibody, along with IVIG was found to reduce the z score for the internal diameter of the coronary artery. 2 We conducted a small, prospective pilot study of tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, for IVIG-resistant Kawasaki's disease.
Baseline characteristics of cancer Patients demanding integrative oncology (IO) support. The experience of Nuova Oncologia Integrata (NOI), an Italian non-profit organization
Authors: L. Bidin, G. Marafante, B. Pellacani, A. Andreoni, G. Macca, E. Fiocchi, L. Boni, G. Cantù, L. Garnerone, R. Sgorbati, F. Putignano, B. Belfiglio, F. Franchi, C. Corda, C. La Guzza, C. Ferri, I. Giuffredi, E. Lamanuzzi, L. Pigaiani, M. Casini, M. Mazzoni
Journal: Annals of Oncology (2017)
Erratum: Selective inhibition of 2-AG hydrolysis enhances endocannabinoid signaling in hippocampus
Authors: Judit K Makara, Marco Mor, Darren Fegley, Szilárd I Szabó, Satish Kathuria, Giuseppe Astarita, Andrea Duranti, Andrea Tontini, Giorgio Tarzia, Silvia Rivara, Tamás F Freund, Daniele Piomelli
Journal: Nature Neuroscience (2006)
CMET-24. EFFICACY AND TOXICITY OF STEREOTACTIC RADIOSURGERY FOR TREATMENT OF PATIENTS WITH 10 OR MORE BRAIN METASTASES
Authors: Steve Braunstein, Michael Garcia, James Scharfen, Lijun Ma, Jean Nakamura, Shannon Fogh, Manish Aghi, Philip Theodosopoulos, Michael McDermott, Penny Sneed
Journal: Neuro-Oncology (2017)

For patients with a limited number (<10) of brain metastases (BM), studies increasingly support excellent disease control with stereotactic radiosurgery (SRS) in lieu of whole brain radiotherapy (WBRT), with potential for improved neurocognitive preservation. With increasing disease burden (≥`10 BM), SRS outcomes remain unclear. We identified 97 patients with 10 or more brain metastases who underwent fixed-frame SRS (FFSRS) without WBRT for newly-diagnosed or recurrent BMs at our institution between September 1998 and December 2013. We reviewed dose-volume metrics, treatment-related outcomes of overall survival (OS), treated lesion freedom from progression (FFP), freedom from new metastases (FFNM), and adverse radiation effect (ARE). Among the patient cohort, the median age was 56 (range 17–84) and median KPS 80 (range 40–90). Primary histologies were predominantly breast, lung, and melanoma. Median number of BM per patient was 12 (IQR 11–16). Median total treatment volume was 4.3 cc (IQR 2.3–11.5 cc). Forty-three patients received FFSRS without WBRT as upfront BM radiotherapy and 54 as salvage therapy after prior WBRT, with median OS 7.8 and 8.8 mo, respectively. FFP at 1 year with 95% confidence intervals for upfront vs. salvage FFSRS was 94% (91–96%) vs. 86% (81–90%) by lesion. FFNM at one year for upfront vs. salvage FFSRS was only 9% (2–22%) vs. 14% (4–30%). At progression, 40 patients received additional FFSRS, 20 (21%) had WBRT, and one had partial brain radiotherapy. Median brain and hippocampal volume receiving 8Gy was less than 10% and 1% respectively. Symptomatic ARE was observed in 1% of 1018 treated lesions over the patients’ disease course. Our institutional experience demonstrates excellent local control following FFSRS for patients with 10 or more BM as upfront therapy or at recurrence following prior WBRT. Hippocampal avoidance can be readily achieved and rates of ARE were modest, consistent with prior studies.
P1.16-008 Near-Infrared Fluorescence-Guided Pulmonary Segmentectomy Following Endobronchial Indocyanine Green Injection
Authors: H. Wada, H. Oheda, K. Nishii, T. Kaiho, K. Ohashi, Y. Shina, Y. Sata, T. Toyoda, A. Hata, Y. Sakairi, H. Tamura, T. Fujiwara, T. Nakajima, H. Suzuki, M. Chiyo, I. Yoshino
Journal: Journal of Thoracic Oncology (2017)
Nab-paclitaxel in clinical practice: data from the MANTEL study
Authors: P. Vanella, O. Garrone, C. Saggia, P. Bergnolo, A. Beano, M. Airoldi, A. Turletti, F. Castiglione, E. Manzin, N. Denaro, E. de Conciliis, A.M. Vandone, M. Donadio, E. Miraglio, M.C. Merlano
Journal: Annals of Oncology (2017)
P3.15-007 A Retrospective Review of Small Cell Lung Cancer (SCLC) Patients Treated at Marmara University Hospital
Authors: A. Eriş, M. Ozturk, F. Dane, E. Bozkurtlar, D. Kocakaya, O. Alan, R. Hasanov, T. Telli, S. Halil, E. Tanrıkulu, P. Yumuk
Journal: Journal of Thoracic Oncology (2017)
Monitoring exercise compliance to a home-based exercise program in advanced heart failure patients
Authors: LS Evangelista, WJ McCarthy, MA Hamilton, K Dracup
Journal: Circulation (2003)

Monitoring Exercise Compliance to a Home-Based Exercise Program in Advanced Heart Failure Patients Lorraine S Evangelista, UCLA Sch of Nursing, Los Angeles, CA; William J Mccarthy, UCLA Psych and Cancer Prevention and Control, Los Angeles, CA; Virginia Erickson, UCLA Sch of Nursing, Los Angeles, CA; Michele A Hamilton, UCLA Sch of Medicine, Los Angeles. CA; Kathleen Dracup; UCSF Sch of Nursing, San Francisco, CA Measuring compliance to exercise is important to clinicians and researchers since inadequate compliance can adversely impact the effectiveness of an intervention. Hence, assessment strategies for compliance, like assessment strategies for other outcomes, must have demonstrated validity and reliability if they are to be employed with confidence. PURPOSE: We conducted this study to (1) determine the reliability of a measure of exercise compliance to a home walking program in heart failure patients using pedometers and exercise diaries; and (2) assess the validity (criterion-related) of pedometers by examining how well they predict improvements in functional status over time METHODS: Exercise compliance was measured in 38 patients (7 4% men) aged 54.1 + 11. 7 years who participated in a home-based exercise program. Each patient was instructed to wear a pedometer on their hip during their waking hours. Daily pedometer scores and duration of walking regimen were recorded for 6 consecutive months. Functional status was measured at baseline and at the completion of the exercise training program using the 6-minute walk test and cardiopulmonary exercise test. A comparison of predicted outcomes as reflected by functional status was made between participants who demonstrated increased pedometer distances (~ 1 O percent change from baseline) and those who showed no change during the 6-month exercise training program. RESULTS: Significant Pearson correlations between the 6 monthly pedometer scores (r= .580- .912, ps.005) demonstrated consistency of the measure across time. Pedometer scores and measures of exercise duration were also correlated (r=.455-.652, ps.005). Patients who showed improvements in their pedometer scores had better functional status at 6-months (see table). CONCLUSION: The results of this study suggest that the pedometer might be a valid indicator of exercise compliance in HF patients who participate in a home-based exercise training program. A Comparison of Functional Status at 6Mmonths Pedometer {distance in miles) Exercise Diary (duration in hours) Six-Minute Walk Test (distance in feet) Peak V02 Max Group 1a Group 2b Group 1a Group 2b Group 1a Group 2b N Mean±SD F statistic P value Group 1a 20 16.8±2.9 Group 2b 18 10.0±1.9 a = patients with 2:10 percent improvement in pedometer scores b = patients with no improvement in pedometer scores
PUB084 Unusual Morphological Variants of Lung Tumors - a Diagnostic Challenge: A Short Series from Eastern India
Authors: P. Mishra, S. Patra, S. Purkait, M. Sable, S. Padhi, M. Sethy, P. Mohapatra, M. Nayak, N. Sahoo, R. Gharei, S. Samal, G. Behera, M. Panigrahi, S. Bhuniya
Journal: Journal of Thoracic Oncology (2017)