tbuckley/cabot-search huggingface dataset:
SLIT1 Mutation in Patients with Acquired Aplastic Anemia: Its Relevance in Immune Pathophysiology
Authors: Chizuru Saito, Kohei Hosokawa, Takamasa Katagiri, Akinori Kanai, Hirotaka Matsui, Toshiya Inaba, Masafumi Taniwaki, Hirohito Yamazaki, Shinji Nakao
Journal: Blood (2012)
Complete response to avelumab in Merkel Cell Carcinoma, and potential correlation with toxicity: a case report
Authors: D. Femia, N. Prinzi, S. Pusceddu, L. Concas, G. Lo Russo, V. Claudio, M. Milione, G. Dinoi, A. Raimondi, P. Michele, D.B. Filippo, R. Buzzoni
Journal: Annals of Oncology (2016)
Phase 3 trial of pixantrone plus rituximab versus gemcitabine plus rituximab in treating relapsed/refractory transplant-ineligible aggressive non-Hodgkin's lymphoma
Authors: P.G. Georgiev, D. Belada, S. Dakhil, L.F. Inhorn, D. Andorsky, A.M. Liberati, J.T. Beck, D. Quick, C. Patti, L. Sivcheva, J.M. Zaucha, R. Pettengell, T. Devries, J.P. Dean, M. Pavlyuk, N. Failloux, K. Hübel
Journal: Annals of Oncology (2016)
Methylated Retroviral Integration Mutagenesis (MRIM) in Mice and Comparative Analysis in Human AML Identify Reduced PTP4A3 Expression As a Prognostic Indicator
Authors: Renee Beekman, Marijke G. Valkhof, Stefan J. Erkeland, Erdogan Taskesen, Veronika Rockova, Justine K. Peeters, Peter Valk, Ivo P. Touw
Journal: Blood (2011)
EXTH-54. TARGETING NEDD8 TO UNCOVER AN EXCEPTIONAL RESPONDER MOLECULAR SUBTYPE IN GLIOBLASTOMA
Authors: Darren Finlay, Peiwen Pan, Seungchan Kim, Gil Speyer, Jeff Kiefer, Harshil Dhruv, Kristiina Vuori, Michael Berens
Journal: Neuro-Oncology (2016)

Neddylation is a post-translational mechanism that marks proteins for degradation through activity of NEDD8 Activating Enzyme (NAE). NAE blocks cullin-RING ligases from initiating proteosomal degradation of select substrates including cell cycle regulators and apoptosis modulators. MLN4924, or Pevonedistat, targets NAE and inhibits Neddylation and induces apoptosis in sensitive cells. We have discovered, in a cohort of glioblastoma PDX models, an exceptional responder. Most pertinently the effects we observe are in a PDX cultured as 3D neurospheres that more closely resemble the true tumor architecture, heterogeneity and the “stem-like” property of spheroid growth. We have leveraged RNAseq expression data from Cancer Cell Line Encyclopedia (CCLE) and Pevonedistat response data from The Cancer Therapeutics Response Portal (CTRP) to apply a network-based analysis to identify pathways enriched with differential dependencies between sensitive and non-sensitive cell lines. The analysis also identifies potential mediating genes that appear to play critical roles in such differential dependency network. Identified differential networks and mediators provide a significant insight for cellular mechanisms underlying drug response. For instance, one pathway identified, “Association of licensing factors with the pre replicative complex,” a known pathway responsive to Neddylation, shows significant differential rewiring between non-sensitive and sensitive cell lines. Additionally, pathways identified are subject to follow up verification. Thus genomic characterization of patient samples may lead to the identification of a subset of patients that may respond to MLN4924. As the treatment options for GBM are extremely limited this may provide a novel alternative opportunity to treat some patients with this aggressive disease.
CagA and NFAT co-operatively participate in the lymphomagenesis of gastric MALT lymphoma
Authors: S.-H. Kuo, H.-J. Tsai, K.-H. Yeh, C.-W. Lin, Y.-S. Zeng, M.-S. Wu, P.-N. Hsu, L.-T. Chen, A.-L. Cheng
Journal: Annals of Oncology (2016)
Dasatinib (Sprycel®) and Low Intensity Chemotherapy for First-Line Treatment In Elderly Patients with De Novo Philadelphia Positive ALL (EWALL-PH-01): Kinetic of Response, Resistance and Prognostic Significance
Authors: Philippe Rousselot, Jean Michel Cayuela, Sandrine Hayette, Christian Récher, Thibaut Leguay, Celia Salanoubat, Francis Witz, Magda Alexis, Mathilde Hunault, Maud Janvier, Philippe Agape, Christian Berthou, Eric Jourdan, José Fernandes, Laurent Sutton, Anne Banos, Oumedaly Reman, Bruno Lioure, Xavier Thomas, Norbert Ifrah, Nicola Gokbuget, Dieter Hoelzer, Andre Delannoy, Renato Bassan, Jose M. Ribera, Sebastian Giebel, Herve Dombret, Oliver G. Ottmann
Journal: Blood (2010)
Delayed initiation of HER2-targeted therapy (HER2Tx) is associated with a higher risk of relapse for early stage (ES) HER2-positive (HER2+) breast cancer (BrCa)
Authors: G. Gullo, R. Bose, N. Walsh, M. Maltese, D. Fennelly, J. Walshe, J. Ballot, J. Crown
Journal: Annals of Oncology (2016)
Comparative miRNA Expression Profiling of Circulating Exosomes From MGUS and Smoldering Multiple Myeloma Patients
Authors: Salomon Manier, Erica N Boswell, Antonio Sacco, Patricia Maiso, Ranjit Banwait, Yosra Aljawai, Xavier Leleu, Aldo M Roccaro, Irene M. Ghobrial
Journal: Blood (2012)
TMOD-28. UNDERSTANDING EGFRvIII GENOMIC BREAKPOINTS THROUGH CRISPR MODELING
Authors: Nathan Jameson, Jorge Benitez, Ciro Zanca, Tomoyuki Koga, Frank Furnari
Journal: Neuro-Oncology (2016)

Glioblastoma multiforme (GBM) is the most common and aggressive adult intracranial tumor accounting for 50% of diagnosed brain tumors every year. Genotypically, GBM’s express a variety of oncogenic mutations and amplifications including the epidermal growth factor receptor, EGFR. EGFR is the most frequently altered gene in GBM, being focally amplified in 40% of primary tumors. In a majority of these amplified EGFR cases, EGFRvIII is also present. The EGFRvIII mutant receptor is caused by recombination between loci in intron 1 and 7 leading to genomic deletion of exons 2-7, resulting in loss of part of the extracellular ligand-binding domain and constitutive signaling activity. Analysis of EGFR utilizing publically available data uncovered strong epigenetic regulatory signals in intron 1. Break points mapped from EGFRvIII deletions in patient samples and GBM cell lines within intron 1 reveal interesting patterns of deletion coordinates, with breakpoints often falling directly upstream of predicted enhancer regions as defined by the presence of strong ChIP-Seq peaks for histone marks H3K27Ac and H3K4me1. Together, these intron 1 enhancers have been identified as super-enhancers in U87 glioma cells. Chromatin interaction data suggests that these regions interact at long distance with the EGFR promoter. Putative enhancer regions in intron 1 are lost to varying degrees based upon the extent of deletion caused by the EGFRvIII mutation, the consequences of which are unknown. Recent data has defined a phenomena known as enhancer hijacking in which genomic deletion leads to a reorganization of the chromatin interactions within a genomic region. In medulloblastoma this results in enhanced expression of potent oncogenes that have been reorganized into close proximity with cell type specific enhancers. Loss of exons 2-7 and any additional intron 1 epigenetic regulation may lead to significant local chromatin reorganization, the consequences of which are unknown and undeterminable using current EGFRvIII models.
BMET-16. REVISED GRADED PROGNOSTIC ASSESSMENT FOR NON-SMALL CELL LUNG CANCER (NSCLC) BRAIN METASTASES (BM) IN THE ERA OF MOLECULAR PROFILING
Authors: Suresh Kumar Balasubramanian, Philipp Schmitt, Samuel Chao, Lilyana Angelov, Alireza Mohamaddi, David Peereboom, John Suh, Xuefei Jia, Gene Barnett, Manmeet Ahluwalia
Journal: Neuro-Oncology (2016)

NSCLC is the most common cause of BM. Activating mutation in EGFR and ALK constitutes 15% and 5% of NSCLC respectively. The Graded Prognostic Assessment (GPA) scale in NSCLCBM doesn’t include activating mutation that is associated with better prognosis. We report the impact of mutations on survival at our tertiary care center. With IRB approval, Cleveland Clinic Brain Tumor Center’s database was queried for NSCLCBM with known mutational status (2000-2015). The primary endpoint was OS from diagnosis of NSCLCBM. Cox proportional hazards models were used for data analysis. Stepwise variable selection was used to identify independent prognostic factors. 348 patients (23 ALK+, 68 EGFR+, 257 wild-type) with median age of 60 years (range 30-93) were included for analysis. KPS was >80 in 143 patients (44%), 70-80 in 144 (44%) and <70 in 37 (11%) patients. Single BM was noted in 152 (44%), 2-3 BM in 94 (27.2%) and >3 BM in 99 (29%) patients. Initial therapy included whole brain radiation (WBRT) +/- Surgery in 164 (47%), stereotactic radiosurgery (SRS) +/- Surgery in 128 (37%), WBRT + SRS in 31 (9%), other treatments were employed in 18 patients (5%). 50% of mutation positive patients received adjuvant targeted therapy. Median OS for ALK and EGFR+ NSCLCBM was 19.9 months vs. 10.1 months in wild-type (p .003). On multivariate analysis, KPS, activating mutation, extracranial metastases (ECM) to bone, lymph nodes and adrenal gland were independent predictors of OS in contrast to conventional GPA. Revised GPA based on KPS, mutational status and presence of ECM was developed with three groups: “unfavorable” (median OS = 3.9 months), “intermediate” (median OS = 12.3 months) and “favorable” (median OS = 24.3 months) (p < .001). A revised DS-GPA for NSCLCBM that includes KPS, mutational status and ECM is proposed.
Center Characteristics and Procedure-Related Factors Have an Impact on Outcomes of Allogeneic Transplantation for Patients with CLL: A Retrospective Analysis from the European Society for Blood and Marrow Transplantation (EBMT)
Authors: Johannes Schetelig, Liesbeth C de Wreede, Niels S. Andersen, Carol Moreno, Michel van Gelder, Antonin Vitek, Michal Karas, Mauricette Michallet, Maciej J Machaczka, Martin Gramatzki, Dietrich W. Beelen, Jurgen Finke, Julio Delgado, Liisa Volin, Jakob Passweg, Peter Dreger, Nicolaas PM Schaap, Matthias Theobald, Anja Henseler, Anja van Biezen, Martin Bornhaeuser, Simona Iacobella, Hein Putter, Stefen Schönland, Nicolaus Kröger
Journal: Blood (2016)
RTHP-35. IMPACT OF TUMOR TREATMENT FIELD ARRAY ON PROTON BEAM DOSE DISTRIBUTION AND IMAGE GUIDANCE IN THE TREATMENT OF CNS MALIGNANCIES
Authors: Howard Morgan, John B. Wilkinson, Matthew Maynard, Joseph Dugas, Hsinsun Wu, Daniel Bonnette, Lane Rosen, Kuanling Chen
Journal: Neuro-Oncology (2016)

Use of tumor treatment fields (TTFs) after radiotherapy and temozolomide for glioblastoma multiforme (GBM) increases survival. Prescribing the TTF system concurrently with radiotherapy may increase disease control. We studied the impact of TTF arrays on proton beam dosimetry and cone-beam CT (CBCT) image quality. Two commercially available TTF arrays were positioned on a Zebra multi-layer ion chamber system and a PBU-50 head phantom. Each TTF array consists of nine ceramic discs encased in plastic with connecting metal wires. Single proton beams at various clinical energies (range: 135-225 MeV) were directed through the ceramic disc component of the TTF array. Depth dose measurements were then obtained for the proton beam to determine the degree of TTF array-associated beam pullback. For IGRT assessment, CBCT images were obtained with the two arrays in place. Image quality and degree of scatter were qualitatively assessed using the contralateral side of the phantom without TTF arrays as an internal control. Measurement of the pristine Bragg peak of a single 145 MeV pencil beam generated by a spot scanning proton therapy system was 14.75 cm. After placement of the TTF array in line with this beam, depth of penetration decreased to 14.03 cm, yielding a pullback of 7.2 mm. Similar results were obtained (range: 7.2-7.3mm) at other energies within our beam’s clinical range. CBCT quality due to a high degree of scatter compromised visualization of the skull of the phantom. If all four arrays were present, CBCT-based image guidance likely would not be possible without modification of the array layout. Use of the TTF system concurrently with proton beam therapy may be possible with alterations in treatment planning and array placement on radiotherapy treatment days. Further clinical study is warranted to determine feasibility and whether an additional clinical effect is possible.
Aberrant SYK Kinase Signaling Is Essential for Tumorigenesis Induced by TSC2 Inactivation
Authors: Ye Cui, Wendy K. Steagall, Anthony M. Lamattina, Gustavo Pacheco-Rodriguez, Mario Stylianou, Pranav Kidambi, Benjamin Stump, Fernanda Golzarri, Ivan O. Rosas, Carmen Priolo, Elizabeth P. Henske, Joel Moss, Souheil El-Chemaly
Journal: Cancer Research (2017)

Somatic or germline mutations in the tuberous sclerosis complex (TSC) tumor suppressor genes are associated closely with the pathogenesis of lymphangioleiomyomatosis, a rare and progressive neoplastic disease that predominantly affects women in their childbearing years. Serum levels of the lymphangiogenic growth factor VEGF-D are elevated significantly in lymphangioleiomyomatosis. However, there are gaps in knowledge regarding VEGF-D dysregulation and its cellular origin in lymphangioleiomyomatosis. Here, we show that increased expression and activation of the tyrosine kinase Syk in TSC2-deficient cells and pulmonary nodules from lymphangioleiomyomatosis patients contributes to tumor growth. Syk kinase inhibitors blocked Syk signaling and exhibited potent antiproliferative activities in TSC2-deficient cells and an immunodeficient mouse xenograft model of lymphangioleiomyomatosis. In TSC2-deficient cells, Syk signaling increased the expression of monocyte chemoattractant protein MCP-1, which in peripheral blood mononuclear cells (PBMC) stimulated the production of VEGF-D. In clinical isolates of PBMCs from lymphangioleiomyomatosis patients, VEGF-D expression was elevated. Furthermore, levels of VEGF-D and MCP-1 in patient sera correlated positively with each other. Our results illuminate the basis for lymphangioleiomyomatosis growth and demonstrate the therapeutic potential of targeting Syk in this and other settings driven by TSC genetic mutation. Cancer Res; 77(6); 1492-502. ©2017 AACR.
RARE-20. PEDIATRIC TECTAL PLATE GLIOMAS WITH PILOMYXOID HISTOLOGIC FEATURES. REPORT OF THREE CASES
Authors: Christine Fuller, Maryam Fouladi
Journal: Neuro-Oncology (2016)

Pediatric tectal plate gliomas (TPG) are generally considered indolent lesions that uncommonly progress. The majority of these patients require cerebrospinal fluid (CSF) diversion via ventriculostomy or shunting, but oftentimes no tissue is retrieved for pathologic diagnosis. The few reports of TPG histology describe mainly low grade astrocytomas, with few reports of ependymoma, malignant glioma, or pilocytic astrocytoma. We have encountered three pediatric TPGs with pilomyxoid histologic features. This cohort includes two females (ages 3.5 and 7 years) and one male (age 3.8 years). All of these children presented with symptoms indicating increased intracranial pressure. Magnetic resonance imagining (MRI) studies confirmed hydrocephalus, and though the dimensions of their individual tectal tumors were variable, all were T1 hypointense, T2 hyperintense, and showed patchy enhancement post contrast administration. A separate fourth ventricular lesion was detected in the male; it had similar MRI signal characteristics to his tectal tumor. All three patients underwent CSF diverting procedures. Both females additionally underwent tectal tumor biopsies, while the male underwent subtotal resection of the fourth ventricular lesion. The entirety of tissue examined from the youngest patient’s tumor consisted of pilomyxoid astrocytoma, typified by a monomorphous population of bland glial cells with long delicate processes, perivascular rosetting, and myxoid background. In contradistinction, the two other tectal lesions exhibited combined features of pilomyxoid astrocytoma and typical pilocytic astrocytoma, the later component with demonstrable Rosenthal fibers and/or eosinophilic granular bodies. Both tumors tested for BRAF duplication/fusion were positive. Post-surgery, all patients were monitored by serial MRI; one developed tectal lesion progression, received chemotherapy, and subsequently recurred a second time, while the male experienced multiple tectal lesion progressions as well as metastatic spread to thecal sac and petrous bone. This unique cohort emphasizes the potential aggressive nature of a subset of pediatric tectal plate gliomas, specifically those with pilomyxoid histology.
Distress assessment in cancer patients in DH setting
Authors: A. Di Liscia, M. Ardizzi, M. Schellino, A. Balbo, A.M. Bandiera, S. Cimino, A. Di Lonardo, M. Floccia, M.L. Mura, F. Salamone, T. Embriaco, R. Ravera, L.M. Repetto
Journal: Annals of Oncology (2016)
EXTH-62. EVALUATION THE EFFECT OF SONODYNAMIC THERAPY WITH 5-ALA AND FOCUSED ULTRAOSUND IN BRAIN TUMOR MODELS
Authors: Chiungyin Huang, Kuochen Wei
Journal: Neuro-Oncology (2016)

To treat brain tumor, using sonodynamic therapy is one of the promising methods. 5-ALA, the product in heme biosynthesis pathway, is able to reentry mitochondria and converted to strongly fluorescent protoporphyrin IX (PpIX) and accumulates in glioma cells. Therefore, the use of 5-ALA guided tumor resection has been reported to improve the resection rate of tumor and increase median survival. For sonodynamic therapy, 5-ALA also serves as sonosensitizer that produces reactive oxygen species to cause cell damage during ultrasound application. It has been reported the use of sonodynamic therapy revealed synergistic antitumor effects in malignant melanoma. However, the effect of sonodynamic therapy in deep seated brain tumor is still unknown. Using transcranial focused ultrasound may able to non-invasively deliver energy to brain and activate sonosensitizer to treat gliomas. In the present study, we used focused ultrasound combined 5-ALA to test the effect of sonodynamic therapy for glioma cells and glioma model animals. Glioma cell U87-MG and LN229 were used for the test. Our results suggested the combination of focused ultrasound and 5-ALA significantly reduced the glioma cell growth both in vitro and in vivo, demonstrated the potential of 5-ALA/focused ultrasound as sonodynamic therapy for glioma treatment.
The role of clinical risk in Low Grade Glioma patients in the era of genomic medicine: a GICNO study
Authors: E. Franceschi, D. De Biase, R. Poggi, S. Bartolini, A. Fioravanti, A. Bacci, M. Zucchelli, E. Zunarelli, R. Depenni, M. Di Battista, G. Crisi, S. Pizzolitto, G. Pasini, C. Dazzi, A. Gamboni, A. Mura, A.A. Brandes
Journal: Annals of Oncology (2016)
Tenofovir has inferior efficacy in adefovir-experienced chronic hepatitis B patients compared to nucleos(t)ide-naïve patients
Authors: Goh Eun Chung, Eun Ju Cho, Jeong-Hoon Lee, Jeong-ju Yoo, Minjong Lee, Yuri Cho, Dong Hyeon Lee, Hwi Young Kim, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon, Fabien Zoulim
Journal: Clinical and Molecular Hepatology (2017)

A recent study reported that entecavir had inferior efficacy in nucleos(t)ide analogue (NA)-experienced chronic hepatitis B (CHB) patients compared to NA-naïve patients. We sought to compare the efficacy of tenofovir disoproxil fumarate (TDF) in NA-experienced and NA-naïve CHB patients.We retrospectively enrolled 252 consecutive patients who had a serum hepatitis B virus (HBV) DNA level greater than 2,000 IU/mL at the initiation of TDF treatment and who received TDF for at least 6 months. Complete virologic suppression (CVS) was defined as undetectable serum HBV DNA. We generated a multivariate Cox proportional-hazard model to examine predictive factors that were independently associated with time to CVS.The mean age of patients was 48.2 years, and the cohort included 181 NA-naïve patients and 71 NA-experienced patients. The median duration of TDF treatment was 14.4 (interquartile range, 9.5-17.8) months. A total of 167 (92.3%) of 181 NA-naïve patients achieved CVS, and 60 (84.5%) of 71 NA-exposed patients achieved CVS. Forty-nine (89.1%) of 55 patients who previously took an NA aside from adefovir and 11 (68.8%) of 16 adefovir-experienced patients achieved CVS. In multivariable analysis, previous adefovir exposure significantly influenced time to CVS (hazard ratio, 0.37; 95% confidence interval, 0.19-0.72; P=0.003), after adjusting for HBeAg positivity, baseline HBV DNA level and cirrhosis.Tenofovir had inferior efficacy in adefovir-experienced CHB patients compared to NA-naïve patients. The response of patients with previous adefovir exposure to TDF monotherapy should be monitored closely.
Increased Risk of Venous Thromboembolism in Primary Central Nervous System Lymphoma Patients Undergoing Therapy
Authors: Gayathri Ravi, Brenda Cooper, Erica L Campagnaro, Basem M. William, Richard J. Creger, Stanton L. Gerson, Marcos De Lima, Hillard M. Lazarus, Paolo Caimi
Journal: Blood (2014)
Efficacy and safety of molecular targeting drugs in patients with metastatic thyroid cancer
Authors: Hirotaka Takasaki, Hiroyuki Iwasaki, Nobuyasu Suganuma, Hironao Okamoto, Kozo Yamamoto, Nobutaka Mizoguchi, Maiko Totsu, Hiromi Kawano, Keiko Masuda, Rika Sakai
Journal: Annals of Oncology (2016)
5-Azacytidine (AZA) Compared to Intensive Chemotherapy in Elderly Acute Myeloid Leukemia (AML) Patients: Results of a Retrospective Single Centre Matched Analysis,
Authors: Elsa Lestang, Sameh Ayari, Patrice Chevallier, Thierry Guillaume, Fanny Rialland, Nicolas Blin, Nadia Fayad, Aline Clavert, Virginie Roland, Thomas Gastinne, Beatrice Mahe, Viviane Dubruille, Steven Le Gouill, Philippe Moreau, Mohamad Mohty, Jacques Delaunay
Journal: Blood (2011)
Prognostic Model for Aggressive Non-Hodgkin Lymphoma.
Authors: Sonja G. Genadieva-Stavrik, Ljube G. Ivkovsi, Gorgi D. Zografski, Borce A. Georgievski, Zlate R. Stojanoski, Aleksandra T. Pivkova, Lidija A. Cevreska
Journal: Blood (2005)
Autologous Heat Shock Protein Peptide Vaccination for Newly Diagnosed Glioblastoma: Impact of Peripheral PD-L1 Expression on Response to Therapy
Authors: Orin Bloch, Michael Lim, Michael E. Sughrue, Ricardo J. Komotar, John M. Abrahams, Donald M. O'Rourke, Anthony D'Ambrosio, Jeffrey N. Bruce, Andrew T. Parsa
Journal: Clinical Cancer Research (2017)

Standard therapy for newly diagnosed glioblastoma (GBM) is surgical resection, followed by concurrent radiotherapy and temozolomide chemotherapy. In this phase II clinical trial, the addition of an autologous heat-shock protein vaccine to standard therapy was evaluated. Tumor-induced immunosuppression, mediated by expression of PD-L1 on tumor and circulating immune cells, may impact the efficacy of vaccination. Expression of PD-L1 on peripheral myeloid cells was evaluated for the first time as a predictor of survival.