tbuckley/cabot-search huggingface dataset:
OS3.6 Optical Biopsies in Neurosurgery: Raman Spectroscopy for the Real-time Identification of Tumours during Surgery
Authors: B. Vaqas, M. Short, I. Patel, U. Faiz, H. Zeng, K. O’Neill
Journal: Neuro-Oncology (2016)

and involves a space occupying necrotic lesion with vasogenic edema and neurological impairment.It was reported that, especially in longterm survivors with metastatic brain tumors treated with radiosurgery, more than half of patients developed DBRN, with median survival of >2.6 years.However, the treatment options for DBRN are still limited to a few drugs like as steroids, anticoagulants, and anti-VEGFA antibody.We can't examine the time-dependent molecular mechanism in the clinical DBRN, because, by reason of the surgical indication, pathological specimens of human DBRN available for a research purpose are confined to the drug-resistant lesions that has brought on neurological worsening in patients.For the present study, therefore, we have developed a stable rodent DBRN model imitating human DBRN, which is applicable in preclinical studies.The aim of this study is to inclusively analyze the gene expression changes in a normal brain from irradiation to emerging of DBRN using that model.MATERIAL & METHODS: In the present study, we used the rodent DBRN model to elucidate its pathophysiological mechanisms.Briefly, ~45 Gy of X-ray irradiation to a rat cerebral hemisphere didn't develop DBRN at all.65 Gy irradiation was able to make coagulative necrotic lesions in the cerebral white matter about 6 months after irradiation (on MRI, Median: 179 d, 95%CI: 164-199 d), which reproduced the histopathological findings of human DBRN.Meanwhile, >80 Gy irradiation developed a large melting necrosis from 2 to 3 months following irradiation.Using microarray, we sequentially and cyclopaedically analyzed the gene expression changes including miRNAs in the 65 Gy-irradiated rat DBRN model.RESULTS: At the peak phase of DBRN (7m after irradiation), 779 genes (mRNAs) were significantly up-or down-regulated in comparison with at the early phase of DBRN (2m after irradiation).In the pathway analysis for these genes, 29 out of 20,717 gene pathways were detected as significantly altered ones such as Chemokine signaling, Type-II interferon signaling, NF-kappa B signaling, mismatch repairing, Renin-angiotensin signaling, HIF1 signaling, EPO receptor signaling, VEGFR signaling, and so on.As for miRNAs, 135 out of 1218 miRNA expressions were significantly altered between early and peak phase of DBRN.In validation qPCR for chemokine genes, CCL2, CCL5, CCL20, CXCL10, CXCL12 were significantly up-regulated at peak phase of DBRN, which was compatible with the result of transcription pathway analysis.CONCLUSIONS: This model would be useful for understanding pathophysiological mechanisms and searching therapeutic molecular targets or diagnostic biomarkers of DBRN. OS3.
P02.05 Peripheral Nerve Sheath Tumor Epidemiology in the South Central Hospital of High Specialty from PEMEX in Mexico
Authors: J. Guerra Mora, M. Cordoba Mosqueda, R. Hernandez Resendiz, I. Loya Aguilar, R. Vicuña Gonzalez, U. Garcia Gonzalez
Journal: Neuro-Oncology (2016)

AbstractIntroduction:The peripheral sheath tumors are part of a large group of neoplasms that range from biologically benign with minimal disorders in life quality to highly malign with life quality deterioration and high mortality. There are subtypes with high prevalence like Schwannomas and some much rarer like the intracranial peripheral nerve sheath tumor which happen to have very bad prognosis. The aim of this study is to describe the epidemiologic and clinical characteristics of patients with peripheral nerve sheat tumors in a hospital of high specialty.Method and materials:Observational study with patients from March 1999 to March 2016 with confirmed diagnosis of peripheral nerve sheath tumor in the electronic files of the South Central Hospital of High Specialty PEMEX. A statistical analysis is made through the SPSS Statistics of the disease in this Institution program.Results:There were 84 patients with the diagnosis of peripheral nerve sheath tumor with a median age of 48.04 years, 65.5% were males, the most common histological type found was the Schwannoma with a 72.6%, followed by senescent Schwannoma 13.1%, neurofibroma 8.3%, and malign peripheral nerve sheath tumor 2.4%. The most frequent location was at the site of cranial nerves, followed by cervical level 27.4%, lumbar 16.7% and thoracic 9.5%. The most common initial symptom was pain in 23.8% of the patients, and the time of the onset of symptoms to the diagnosis was 31.6 months. From the total of patients 8.3% had neurofibromatosis type 1, 6.0% neurofibromatosis type 2.Conclusions:We realized in our series of reported cases that the frequency is similar to those reported in worldwide population; nevertheless the time between the onset of symptoms and the diagnosis is much higher in our cases as well as the population of patients with neurofibromatosis. This study justifies the need of attention quality improvement and the knowledge of this information the medical doctor of first contact so that the right diagnosis can be made and the treatment given in the shortest time possible.
The FUNNEL: a precision medicine project for metastatic colorectal cancer
Authors: S. Marsoni, S. Siena, C. Martino, I. Depetris, A. Sartore-Bianchi, F. Di Fabio, A. Ponzetti, I. Fioroni, S. Lonardi, P. Cassoni, M. Truini, M. Fiorentino, A. Crescenzi, M. Rugge, F. Leone, P. Racca, V. Zagonel, F. Ciardiello, A. Sapino, M. Aglietta
Journal: Annals of Oncology (2016)
More than 5000 patients with metastatic melanoma in Europe per year do not have access to new life-saving drugs
Authors: L. Kandolf Sekulovic, K. Peris, A. Hauschild, L.V. Demidov, P. Nathan, C. Lebbe, C. Hoeller, C. Blank, J. Olah, H. Gogas, R. Dummer, L. Bastholt, D. Herceg, A. Stratigos, B. Neyns, J. Hansson, P. Rutkowski, A.-M. Forsea, I. Krajsová, C. Garbe
Journal: Annals of Oncology (2016)
Human Cord Blood-Derived Endothelial Progenitor Cells Engraft Following In Utero Transplantation, Integrate into the Developing Cytoarchitecture and Contribute to Ongoing Vasculogenesis.
Authors: Joshua A. Wood, Evan Colletti, Laura E. Mead, David A. Ingram, Christopher D. Porada, Esmail D. Zanjani, Mervin C. Yoder, Graça Almeida-Porada
Journal: Blood (2007)
NIMG-02. CORTICAL PLASTICITY OF MOTOR-ELOQUENT AREAS MEASURED BY NAVIGATED TRANSCRANIAL MAGNETIC STIMULATION IN GLIOMA PATIENTS
Authors: Sandro M. Krieg, Sebastian Ille, Neal Conway, Noemi Wildschuetz, Lucia Bulubas, Nico Sollmann, Noriko Tanigawa, Bernhard Meyer
Journal: Neuro-Oncology (2016)

Better understanding of the mechanisms behind cerebral plasticity, coupled with non-invasive detection of its presence, harbors a huge potential to improve glioma therapy. Our aim was to demonstrate the frequency of plastic reshaping, find patterns behind it, and prove it can be recognized non-invasively using navigated transcranial stimulation (nTMS). We used nTMS to map cortical motor representation in 22 patients with gliomas affecting the precentral gyrus immediately pre-op, and 3-42 months post-op. Location changes of the primary motor area, defined as hotspots and map centers of gravity, were measured. Spatial normalization of nTMS and MRI data showed an average primary motor area shift of 4.7 ± 0.8mm standard error of the mean (SEM) on the mediolateral axis, and 9.7 ± 1.5mm SEM on the anteroposterior axis. Motor-eloquent points tended to shift towards the resection cavity by 4.5 ± 3.6mm SEM if the lesion was anterior to the rolandic region and by 2.6 ± 3.4mm SEM if it was located more posteriorly. Overall, 8 out of 16 (50%) high-grade and 3 out of 6 (50%) low-grade glioma patients showed a functional shift of over 10 mm at the cortical surface level. Despite the series’ small size, analysis of these data shows impressively that cortical functional reorganization occurs quite frequently. Moreover, nTMS is shown to detect such plastic reorganization non-invasively. However, since tumor- and deficit-related subgroups might show different patterns, multicentric analysis of a larger cohort seems compulsory. This provides further motivation to join our newly founded multicentric international study group.
TMIC-30. ROLE OF MATRIX METALLOPROTEINASE 9 (MMP9) IN RESISTANCE TO ANTI-ANGIOGENIC THERAPY
Authors: Garima Yagnik, Ruby Kuang, Arman Jahangiri, William Chen, Manish Aghi
Journal: Neuro-Oncology (2016)

While bevacizumab initially showed great promise as an anti-angiogenic therapy for glioblastoma, randomized clinical trials showed limited duration of efficacy that fails to impact overall survival. Preclinical studies from our group and others found tumors resistant to anti-angiogenic therapy to be more invasive with an increased metastatic potential. This enhanced level of malignant cell invasion is thought to occur through hijacking of natural epithelial-to-mesenchymal transition (EMT) pathways activated during development, a set of complex spatial and temporal interactions for migration involving multiple cellular pathways and transcription factors. To better understand the mechanisms of glioblastoma resistance to anti-angiogenic therapy, we developed a generational xenograft model of resistance and profiled transcriptional changes and cells in the microenvironment contributing to resistance. Genome-wide expression profile of selected generations discovered a shift over time towards a mesenchymal molecular profile, with a similar shift seen in pre- and post-bevacizumab treated patient samples. Detailed analysis of the protein interactions between these mesenchymal genes elucidated MMP9, a member of the matrix metalloproteinase family, as the strongest potential driver of the shift towards the mesenchymal phenotype in our xenograft model. Previous work has found that neutrophils, drawn to inflamed tumors sites, are unique producers of MMP9 without its regulator TIMP1. Fluorescent imaging of intracranial xenograft tumors treated with PBS or bevacizumab discovered increased levels of MMP9, which occurred within the higher number of neutrophils seen in the invading edge of the tumor mass in bevacizumab-treated samples, confirming these tumors are better able to recruit neutrophils and hijack their innate immune response machinery for increased tumor survival. These findings challenge the ideas that gelatinases are solely downstream targets of higher level regulators and that neutrophils are passive inflammatory bystanders, instead defining neutrophil-secreted MMP9 as an early activator responsible for downstream effects driving resistance to anti-angiogenic therapy.
The socioeconomic burden of ovarian cancer in Spain
Authors: L. Delgado-Ortega, A.G. Domínguez, C. Moya-Alarcón, Á Hidalgo, L. Cordero, M. Jiménez, A. Gascó, R. Villoro, J. Borras, E. González-Haba, S. Menjón, J. Oliva, P. Pérez, D. Vicente
Journal: Annals of Oncology (2016)
Genomic alterations in circulating tumor DNA (ctDNA) are associated with clinical outcomes in treatment-naive metastatic castration-resistant prostate cancer (mCRPC) patients commencing androgen receptor (AR)-targeted therapy
Authors: A.W. Wyatt, M. Annala, K. Beja, S. Parimi, G. Vandekerkhove, E. Warner, M. Zulfiqar, D. Finch, C. Oja, J. Vergidis, M. Nykter, M.E. Gleave, K. Chi
Journal: Annals of Oncology (2016)
NIMG-01. A CASE REPORT OF NEUROSARCOIDOSIS PRESENTING AS A LYMPHOMA MIMIC
Authors: Gurcharanjeet Kaur, Lauren Cameron
Journal: Neuro-Oncology (2016)

To describe a unique presentation of neurosarcoidosis. Sarcoidosis is a multisystem disease which involves formation of inflammatory lesions known as granulomas. Central nervous system involvement is rare. Sarcoidosis can be severe and mistaken for systemic lymphoma. 55 year-old right handed white male with OSA, Arthritis, Raynaud’s, Hashimoto’s thyroiditis, was noted to have cognitive decline over a few weeks’ duration, as well as 20lb weight loss. His neurologic exam was normal except five-minute recall. He underwent EEG, CT head, MRI Brain, and MRI PET brain. EEG was normal. Head CT revealed a lacrimal gland mass, confirmed by a contrast brain MRI, which was suspicious for lymphoma on PET MRI brain. Subsequent body PET CT scan showed prominent hypermetabolic lesion in the right lateral orbit, lymph nodes in bilateral neck, axillary regions, chest, pelvis and inguinal regions most consistent with lymphoma. Bone marrow biopsy was negative. Serum and CSF ACE was normal. Supraclavicular lymph node biopsy revealed multiple non-caseating granulomas, diagnostic of “Sarcoidosis”. He was treated with daily prednisone for two months followed by weekly infliximab. MRI brain two months post treatment showed a decrease in size of lacrimal lesion, and PET Brain MRI showed a normal metabolism pattern after five months. CT Chest without contrast showed marked improvement in adenopathy. Neurocognitive evaluation three months after diagnosis demonstrated improvements in memory abilities. Our patient did not have Lymphoma, and had a good response to corticosteroids and infliximab. However, his clinical presentation raised suspicion for lymphoma. Biopsy in these types of cases is necessary to establish correct diagnosis. Neurosarcoidosis has no known cure. Immunosuppression is the principal method of treatment, and corticosteroids are the cornerstone of therapy.
ATP11B mediates platinum resistance in ovarian cancer
Authors: Myrthala Moreno-Smith, J.B. Halder, Paul S. Meltzer, Tamas A. Gonda, Lingegowda S. Mangala, Rajesha Rupaimoole, Chunhua Lu, Archana S. Nagaraja, Kshipra M. Gharpure, Yu Kang, Cristian Rodriguez-Aguayo, Pablo E. Vivas-Mejia, Behrouz Zand, Rosemarie Schmandt, Hua Wang, Robert R. Langley, Nicholas B. Jennings, Cristina Ivan, Jeremy E. Coffin, Guillermo N. Armaiz, Justin Bottsford-Miller, Sang Bae Kim, Margaret S. Halleck, Mary J.C. Hendrix, William Bornman, Menashe Bar-Eli, Ju-Seog Lee, Zahid H. Siddik, Gabriel Lopez-Berestein, Anil K. Sood
Journal: Journal of Clinical Investigation (2013)

The legend for Figure 5 did not disclose that the images presented in part A were duplicated as the no treatment control for the cisplatin experiment shown in parts D and E. The authors wish to add the correction below to the legend for Figure 5.The merged immunofluorescence images showing colocalization of ATP11B and STX6 in A2780-PAR and A2780-CP20 cells in A are shown again in D and E to demonstrate localization of ATP11B and STX6 in the absence of cisplatin in A2780-PAR and A2780-CP20 cells.
P06.02 Transcriptional profiling to identify determinants associated with response to ABT-414 in patients with glioblastoma
Authors: M. van den Bent, H. Gan, D. A. Reardon, K. P. Papadopoulos, R. Merrell, P. Kumthekar, L. Roberts-Rapp, K. Holen, P. Ansell, A. B. Lassman
Journal: Neuro-Oncology (2016)
PULSE, a phase 2 study of mFOLFOX6-panitumumab (P) with biomarker stratification as first-line chemotherapy (CT), in patients (pts) with KRAS (exon 2) metastatic colorectal cancer (mCRC). A GEMCAD 09-03 study
Authors: J. Maurel, C. Fernández Martos, M. Martín Richard, V. Alonso, C. Méndez Méndez, A. Salud, C. Pericay, J. Aparicio, J. Gallego, A. Carmona, E. Casado, H. Manzano, C. Horndler, M. Rubini, M. Cuatrecasas, X. García-Albéniz, J. Feliu
Journal: Annals of Oncology (2016)
Results of a prospective, multicenter, non-interventional trial to analyze disease- and treatment-related effects on the functionality of patients with gastrointestinal tumors ≥ 75 years
Authors: J. Hofmann, N. Härtel, J. Hofmann, M. Neugebauer, A. Berger, S. Zschäbitz, H. Schulze-Bergkamen, J. Betge, S. Belle, R. Jesenofsky, N. Schulte, U. Wedding, M. Ebert, J. Chi-Kern
Journal: Annals of Oncology (2016)
Long noncoding AGAP2-AS1 is activated by SP1 and promotes cell proliferation and invasion in gastric cancer
Authors: Fuzhen Qi, Xianghua Liu, Hao Wu, Xiang Yu, Chenchen Wei, Xiaodan Huang, Guozhong Ji, Fengqi Nie, Keming Wang
Journal: Journal of Hematology & Oncology (2017)

Long noncoding RNAs (lncRNAs) have emerged as important regulators of tumorigenesis and cancer progression. Recently, the lncRNA AGAP2-AS1 was identified as an oncogenic lncRNA in human non-small cell lung cancer (NSCLC) and its elevated expression was linked to NSCLC development and progression. However, the expression pattern and molecular mechanism of AGAP2-AS1 in gastric cancer (GC) have not been characterized.Bioinformatic analysis was performed to determine AGAP2-AS1 expression levels in the GC and normal tissues using gene profiling data from the Gene Expression Omnibus. Quantitative real-time polymerase chain reaction was used to validate AGAP2-AS1 expression in the GC tissues/cell lines compared with that in the adjacent nontumorous tissues/normal epithelial cells. Loss- and gain-of-function approaches were performed to investigate the effect of AGAP2-AS1 on GC cell phenotypes. The effect of AGAP2-AS1 on cell proliferation was evaluated by MTT, colony formation, flow cytometry, and in vivo tumor formation assays. The effects of AGAP2-AS1 on cell migration and invasion were examined using Transwell assays. Chromatin immunoprecipitation, luciferase reporter assays, RNA pull-down, and RNA immunoprecipitation were used to investigate the factors involved in AGAP2-AS1 dysregulation and the mechanism of action of AGAP2-AS1 in the GC cells.AGAP2-AS1 was highly expressed in the GC tissues and cell lines, and patients with higher AGAP2-AS1 expression had a poorer prognosis and shorter overall survival. Furthermore, knockdown of AGAP2-AS1 significantly inhibited GC cell proliferation, migration, and invasion in vitro and tumor growth in vivo. AGAP2-AS1 overexpression promoted cell growth and invasion. In addition, the transcription factor SP1 activated AGAP2-AS1 expression in the GC cells. AGAP2-AS1 functions as an oncogenic lncRNA by interacting with LSD1 and EZH2 and suppressing CDKN1A (P21) and E-cadherin transcription.Taken together, these findings imply that AGAP2-AS1 upregulated by SP1 plays an important role in GC development and progression by suppressing P21 and E-cadherin, which suggests that AGAP2-AS1 is a potential diagnostic marker and therapeutic target for GC patients.
IMST-51. DEVELOPMENT OF A PEPTIDE VACCINE PLATFORM FOR BRAIN TUMOR IMMUNOTHERAPY THAT INCORPORATES ADJUVANT CD27 STIMULATION FOR ENHANCED T CELL IMMUNITY
Authors: Katherine Riccione, Luis Riccione, John H. Sampson
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is the most common malignant primary brain tumor and the most fatal, despite aggressive multimodal standard of care. Immunotherapy with peptide vaccines derived from tumor antigens allows for tumor-specific killing while sparing normal brain. However, the broad success of peptide vaccines is limited by their ability to induce potent CD8+ T cell responses. Immunomodulatory antibodies that promote costimulatory signaling offer a broad adjuvant strategy for potentiating peptide-induced immunity. This research evaluates the mechanism by which an immunomodulatory agonist antibody specific for the T cell costimulatory molecule CD27 enhances the immune response to peptide vaccination for brain tumor immunotherapy. CD27 is constitutively expressed on naïve T cells, and signaling through this pathway during concomitant antigen presentation promotes T cell proliferation and survival and upregulation of pro-inflammatory cytokines. Furthermore, CD27 stimulation decreases the threshold of T cell activation to low-affinity antigens, suggesting a role for this pathway in promoting robust antitumor immunity. Celldex Therapeutics has developed a clinically-relevant high-affinity human-anti-human CD27 monoclonal antibody (αhCD27) that induces potent human T cell responses and prolongs survival in human CD27 transgenic mice bearing subcutaneous tumors. Here, we evaluate αhCD27 as a vaccine adjuvant against a model tumor antigen. We show that αhCD27 enhances the vaccine-induced T cell response and prolongs survival of mice bearing intracranial tumors in a T cell-dependent fashion. Interestingly, we demonstrate that the enhanced αhCD27-mediated vaccine-induced CD8+ T cell response is dependent upon CD27 stimulation on antigen-specific CD4+ T cells generated via MHC class II epitopes provided by the vaccine, indicating that the vaccine composition considerably influences the adjuvant potential of αhCD27. We demonstrate that this mechanistic information can be leveraged to develop a synthetic peptide vaccine platform targeting both CD4+ and CD8+ T cells against clinically-relevant antigens, such that the adjuvant potential of αhCD27 is optimally exploited.
Pertuzumab, Trastuzumab, Docetaxel: a single istitution clinical exeperience for Her2 positive metastatic breast cancer (mBC)
Authors: C. Martines, G. Lavenia, P. Salice, F. Latteri, O. Commendatore, D. Sambataro, G. Burrafato, M. Mattina, P. Amadio, R. Bordonaro
Journal: Annals of Oncology (2016)
Intensive Chemotherapy (LMB-86 Regimen) for AIDS-Related Burkitt’s Lymphoma/Leukemia.
Authors: Lionel Galicier, Claire Fieschi, Laurence Gerard, Sylvie Chevrey, Emmanuelle Boulanger, Marie-Therese Daniel, Veronique Meignin, Eric Oksenhendler
Journal: Blood (2005)
Efficacy and Safety of Everolimus in Advanced Nonfunctional Neuroendocrine Tumors (NET) of Lung or Gastrointestinal (GI) Origin: Findings From the Asian Subgroup Analysis of the RADIANT-4 Study
Authors: James C. Yao, Do-Youn Oh, Jiaming Qian, Young Suk Park, Herbst Fabian, Ridolfi Antonia, Tetsuhide Ito, Liqun Jia, Izumi Komoto, Virote Sriuranpong, Yasuhiro Shimada
Journal: Annals of Oncology (2016)
EXTH-18. REPURPOSING IBUDILAST IN COMBINATION WITH TEMOZOLOMIDE FOR GLIOBLASTOMA
Authors: Kerrie McDonald, Wendy Ha, Hatice Sevim Nalkiran, Mustafa Khasraw
Journal: Neuro-Oncology (2016)

Recurrence in patients with Glioblastoma (GBM) is inevitable, even in patients with O-6-Methylguanine-DNA Methyl Transferase (MGMT) methylation. We identified increased expression of the inflammatory cytokine, Macrophage Inhibitory Factor (MIF) and its receptor CD74 in patients with recurrent tumors. High levels of MIF and CD74 were associated with poor overall survival in glioblastoma patients. This study aims to determine efficacy of Ibudliast (AV411; 3-isobutyryl-2-isopropylpyrazolo-[1,5-a]pyridine) to block MIF expression and decrease tumor burden. Ibudilast is an anti-inflammatory drug that was developed for the treatment of bronchial asthma. The patient derived cell lines (PDCLs) RN1 (MGMT unmethylated), BAH1 (MGMT methylated), and HW1 (MGMT methylated) were treated in vitrowith different concentrations of ibudilast in combination with temozolomide (TMZ). Patient derived xenograft (PDX) models of GBM were developed and also treated with ibudilast in combination with TMZ. Overall survival was calculated. Regardless of MGMT status, significant synergism between ibudilast and TMZ was observed in the PDCLs. Efficacy was associated with significantly decreased expression of its targets, MIF and CD74. Downstream proteins such as Src and Akt were also significantly inhibited. The combination induced apoptosis. RN1 and HW1 tumors were established intracranially in Balb/c nude mice. Significant increases in survival times of the mice were recorded when treated with the combination. Ibudilast in combination with TMZ resulted in significant blockage of MIF expression, increased apoptosis and longer survival in vivo. A phase I/II clinical trial for recurrent GBM patients is warranted.
Conditional Survival and Cause-Specific Mortality in Patients Undergoing Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Hematologic Malignancy Over Three Decades
Authors: Saro H. Armenian, Can-Lan Sun, Tabitha Vase, George Mills, Liezl Atencio, Liton Francisco, Jocelynne Palmer, Ari VanderWalde, F. Lennie Wong, Joseph Rosenthal, Neil Martin Kogut, Leslie Popplewell, David S. Snyder, Anthony Selwyn Stein, Margret O'Donnell, Stephen J. Forman, Smita Bhatia
Journal: Blood (2012)