tbuckley/cabot-search huggingface dataset:
New TET2, ASXL1 and CBL Mutations Have Poor Prognostic Impact In Systemic Mastocytosis and Related Disorders
Authors: Fabiola Traina, Ania Jankowska, Hideki Makishima, Fred H. Hsieh, Yingchun Han, Christine O'Keefe, Yuka Sugimoto, Sanjay R. Mohan, Hadrian Szpurka, Courtney Prince, Kathryn Guinta, Mikkael A. Sekeres, Matt Kalaycio, Alan E. Lichtin, Anjali S. Advani, Edward Copelan, Ronald Sobecks, Jaroslaw P. Maciejewski, Ramon V. Tiu
Journal: Blood (2010)
IMST-42. FIRST PROOF-OF-PRINCIPLE STUDY OF A NOVEL MINIMALLY INVASIVE BLOOD-BASED DIAGNOSTIC TOOL FOR GLIOMA
Authors: Wouter van den Bossche, Arnaud Vincent, Alberto Orfao, Clemens Dirven, Martine Lamfers, Jacques van Dongen
Journal: Neuro-Oncology (2016)

Diagnosing glioma and monitoring tumour progression and treatment efficacy is usually invasive (biopsy or operation) and often needs extensive and time-consuming MRI imaging. Alternative easy, quick and minimally-invasive diagnostic methods are therefore highly warranted. Novel insights in the role of several immune subsets in tissue damage caused by glioma, have prepared the way for a novel blood-based diagnosis and monitoring tool. EuroFlow-based 8-color flow cytometry and multidimensional analysis was used to link immune cell populations in gliomas with leukocyte lineages in the blood of glioma patients. Additionally tumour material and blood leukocytes were investigated by immunocytochemistry to confirm our hypothesis. Based on the obtained results a large patient study including 232 glioma patients of different grades, 19 cerebral metastasis patients and 20 healthy controls was performed to test the applicability of the here proposed diagnostic tool. When the analysis of all patients has been performed, our studies will provide the first Proof-of-Principle for a new minimally-invasive glioma diagnostic and monitoring tool using only a small amount of blood. ELISA data and extensive immunophenotyping of tumour and blood for several leukocyte subsets have already demonstrated the potential of flow cytometric analysis for specific markers on leukocyte subsets. We are awaiting the final results of our large patient study to confirm our current findings and investigate the clinical applicability of this tool. If our results are indeed confirmed, this method will offer a quick and minimally invasive diagnostic tool in neuro-oncology that can be used to diagnose, stage and monitor brain tumors. We expect to have finalized all clinical analyses by the beginning of August.
Phase Ib Study (GO28440) of Venetoclax with Bendamustine/Rituximab or Bendamustine/Obinutuzumab in Patients with Relapsed/Refractory or Previously Untreated Chronic Lymphocytic Leukemia
Authors: Stephan Stilgenbauer, Franck Morschhauser, Clemens-Martin Wendtner, Guillaume Cartron, Michael Hallek, Barbara F. Eichhorst, Mark Kozloff, Thomas A. Giever, Gerard Lozanski, Elizabeth A. Punnoose, Jue Wang, James Hilger, Mehrdad Mobasher, Gilles Salles
Journal: Blood (2016)
CSIG-17. COMPENSATORY ACTIVATION OF STAT3 TRIGGERED BY EGFR INHIBITION: A MECHANISM OF RESISTANCE IN GBM BRAIN TUMOR INITIATING CELLS
Authors: Katharine Jensen, H. Artee Luchman, Samuel Weiss
Journal: Neuro-Oncology (2016)

Despite advances in delineating the mutations and aberrant signaling pathways underlying glioblastoma multiforme (GBM), the prognosis for GBM patients remains dismal. New therapeutic options are desperately needed in order to make this devastating disease manageable. In cancer cells, when one survival signaling pathway is inhibited, network redundancy leads to compensatory mechanisms that activate other survival/proliferation pathways. This mechanism may explain the poor clinical translation of EGFR inhibitors in GBM to date. JAK2/STAT3 signaling is important for tumor cell survival, growth, and invasion and becomes trans-activated upon EGFR inhibition. Given that both EGFR and JAK2/STAT3 are crucial signaling hubs in GBM, if targeted concurrently, this may provide the survival advantage that monotherapies have failed to offer. To test this hypothesis, we examined the actions of the JAK2 inhibitor pacritinib in combination with the EGFR inhibitor afatinib on GBM brain tumor initiating cells (BTICs). STAT3 activation triggered by EGFR inhibition was confirmed in multiple BTIC lines. Protein and mRNA levels of STAT3 and IL6 were found to increase, highlighting a possible mechanism of resistance to EGFR inhibition. We demonstrated that concurrent inhibition of STAT3 and EGFR exhibited striking responses, with extensive synergy and dramatic decreases in BTIC viability and sphere-forming capacity. Western blotting assays showed that the increased phospho-STAT3 observed with EGFR inhibition was abolished with combined treatment. Consistent with in vitro results, EGFR inhibition with afatinib induced an increase in phospho-STAT3 in vivo, in BTIC orthotopic xenografts. This increase was abolished with the combination of afatinib and pacritinib. These data suggest that, in GBM, EGFR inhibition remains of high therapeutic relevance, when combined with inhibition of other pro-oncogenic pathways. Our ongoing studies are aimed at further understanding the mechanism by which STAT3 is activated upon EGFR inhibition and the translational potential of inhibiting these two pathways in combination.
A phase I, open-label, multi-center, dose escalation study of oral NVP-CGM097, a p53/HDM2-protein-protein interaction inhibitor, in adult patients with selected advanced solid tumors
Authors: S. Bauer, G. Demetri, S. Jeay, R. Dummer, N. Guerreiro, D.S. Tan, A. Kumar, C. Meille, L. Van Bree, E. Halilovic, J.U. Wuerthner, P. Cassier
Journal: Annals of Oncology (2016)
Quality-of-Life Changes and Hearing Impairment
Authors: Cynthia D. Mulrow, Christine Aguilar, James E. Endicott, Michael R. Tuley, Ramon Velez, Walter S. Charlip, Mary C. Rhodes, Judith A. Hill, Louis A. DeNino
Journal: Annals of Internal Medicine (1990)

Abstract Objective:To assess whether hearing aids improve the quality of life of elderly persons with hearing loss. Setting:Primary care clinics at a Bureau of Veterans Affairs hospital. Patients:O...
Identification of Highly Clonal Cells in CD34+ and Unselected Bone Marrow Samples From Patients with Myelodysplastic Syndrome Using a Sensitive Quantitative PCR Approach.
Authors: Maximilian Mossner, Daniel Nowak, Ouidad Benlasfer, Jana Reins, Olaf Joachim Hopfer, Claudia D Baldus, Eckhard Thiel, Wolf-Karsten Hofmann
Journal: Blood (2009)
Cytotoxic T Lymphocytes (CTL) Specific for CMV, Adenovirus, and EBV Can Be Generated From Naive T Cells for Adoptive Immunotherapy.
Authors: Patrick Hanley, Barbara Savoldo, Conrad Russell Young Cruz, Ann M. Leen, Jeffrey J. Molldrem, Hao Liu, Adrian P. Gee, Helen E. Heslop, Gianpietro Dotti, John Rodgers, Cliona M Rooney, Malcolm K. Brenner, Elizabeth J. Shpall, Catherine M. Bollard
Journal: Blood (2009)
Development of proteinuria and focal segmental glomerulosclerosis during direct‐acting antiviral therapy for hepatitis C virus infection
Authors: Jonathan J. Hogan, Mary Ann Lim, Matthew B. Palmer, Roy D. Bloom, Raymond T. Chung, Meghan E. Sise
Journal: Hepatology (2017)

Hogan, Jonathan J.; Lim, Mary Ann; Palmer, Matthew B.; Bloom, Roy D.; Chung, Raymond T.; Sise, Meghan E. Author Information
Hematopoietic Cell Transplantation Comorbidity Index As Prognostic Variable in Patients with Invasive Fungal Infections
Authors: Alessandro Busca, Roberto Passera, Enrico Maffini, Lucia Brunello, Chiara Maria Dellacasa, Semra Aydin, Chiara Frairia, Sara Manetta, Sara Butera, Giorgia Iovino, Luisa Giaccone, Mario Boccadoro, Umberto Vitolo, Benedetto Bruno
Journal: Blood (2015)
BSTM-01. LONG-TERM OUTCOME OF SKULL BASE CHORDOMAS IN CHILDREN AND ADOLESCENTS
Authors: Marcio Rassi, Maher Hulou, Kaith Almefty, Wenya Linda Bi, Svetlana Pravdenkova, Ian Dunn, Timothy Smith, Ossama Al-Mefty
Journal: Neuro-Oncology (2017)

INTRODUCTION: Skull base chordomas in patients under 20 years of age are extremely rare. Their course, management, and outcome have not been defined. We highlight the distinguishing clinical and radiological characteristics in a series of pediatric patients with skull base chordomas and analyze the outcome of a cohort who underwent uniform treatment. We emphasize the predictors of overall and progression-free survival, which aligns with Collins’ law for embryonal tumors. METHODS: Thirty-one patients with a mean age of 10.7 years (range 0.8–22) harboring skull base chordomas were evaluated by the senior author (OA) between 1993 and 2008. We retrospectively analyzed the outcomes and prognostic factors for 18 patients that were treated by this surgeon, with a uniform management of surgery with the aim at gross-total resection followed by proton-beam radiotherapy. Mean follow-up was 119.2 months (range 8–263). RESULTS: Abducens nerve palsy was the most prevailing symptom at presentation. Imaging disclosed large tumors that often involve multiple anatomical compartments. Patients undergoing gross total resection had significantly increased progression-free survival (p=0.02) and overall survival (p=0.05) compared with those having subtotal resection. Those who lived through the period of risk for recurrence without disease progression had a higher probability of living entirely free of progression (p=0.03; odds ratio=16.0). Age, sex, and histopathological variant did not yield statistical significance in survival. CONCLUSIONS: Long-term overall and progression-free survival in children harboring skull-base chordomas can be achieved with gross surgical resection and adjuvant proton-beam radiotherapy, despite an advanced stage at presentation. Collins’ law does apply to pediatric skull base chordomas, and children with this disease have a high hope for a cure.
Stage specific survival is altered by the changes in the 2002 AJCC staging for melanoma
Authors: L. Ben-Porat, K. S. Panageas, C. Hanlon, A. Patel, A. N. Houghton, A. C. Halpern, D. G. Coit
Journal: Journal of Clinical Oncology (2005)

7510 Purpose: To examine how stage specific survival is altered in the 2002 American Joint Committee on Cancer (AJCC) melanoma staging system compared to the 1997 AJCC staging system. Patient and Methods: 5,847 consecutive patients presented with melanoma to Memorial Sloan Kettering Cancer Center (MSKCC) from 1996 to 2004 and were prospectively entered into a database. These patients were staged under both the 1997 and 2002 AJCC staging criteria. Overall survival estimates were determined using the Kaplan-Meier method. Results: 1,035 patients were shifted to a lower stage in the 2002 staging system while only 15 patients were upstaged. The number of stage I patients increased greatly under the 2002 system (n=2,166) as compared to the 1997 system (n=1,463) although stage I survival probability estimates were virtually the same with both classification systems. As a result of the changes in 2002, the stage II survival estimates decreased considerably with a 15% lower 5 year overall survival (79% (1997) versus 64% (2002)). With the initiation of subgroups in 2002, it became apparent that stage III patients were very heterogeneous in terms of their survival probabilities (5 year overall survival ranged from 70% in IIIA to 24% in IIIC). Conclusions: Stage specific survival was substantially altered by the changes made in the 2002 AJCC staging for melanoma, particularly for stage II. It is very important to be aware of this effect so that accurate conclusions can be drawn with regard to treatment efficacy or comparisons across different studies. In addition, stage subgroups were added in 2002 that demonstrated the diversity of risk within stage group and did not improve prediction ability. This highlights the importance of developing individualized risk prediction models. No significant financial relationships to disclose.
ATIM-12. A METHOD TO CLASSIFY HUMAN ASTROCYTOMA CELL USING MULTIPARAMETRIC FLOW CYTOMETRY: A STEP TOWARDS SINGLE-CELL MOLECULAR PATHOLOGY OF SOLID TUMORS
Authors: Rachel Grossman, Ilan Volovitz, Netanel Shapira, Zvi Ram
Journal: Neuro-Oncology (2016)

Multicolor flow cytometry (FCM) has revolutionized the molecular pathology of hematological tumors enabling multiparametric classification of single tumor cells. Meanwhile, the pathological evaluation of brain tumors (BTs) and other solid tumors, relies heavily on subjective histopathological evaluation of tissue slices stained for single antigens. To date, no FCM based method has been developed to classify human astrocytoma. Human brain lesions were dissociated to single cells. The cells were analyzed using a five-color FCM staining panel concurrently monitoring Ki67 (a proliferation marker), GFAP (a glial marker) IL13 receptor a2 -IL13Ra2 (a glioma-associated antigen - GAA), A2B5 (a GAA and a chemoresistance marker), and cellular viability. The Tumor-panel enabled blind classification of brain lesions to astrocytomas, to metastasis reaching the brain and to nontumorous lesions based on marker co-expression patterns consistent with the cells’ biology. The panel enabled quantification of the viable tumor cell fraction in lesions following enzymatic dissociation to single-cells and following a tumor-cell purification step using a density gradient. A clinically-relevant finding that emerged from the multiparametic analysis of antigen coexpression in gliomas was the partial co-expression of IL13Ra2 and Ki67: many Ki67+ (proliferating) cells did not express the IL13Ra2 GAA (i.e., IL13Ra2-Ki67+). This may partially explain the failure of several clinical trials that had targeted toxins to gliomas via IL13Ra2. FCM can be used to classify astrocytoma cells within single-cell dissociated brain lesions. The developed method represents a first step towards a quantitative, user-independent means for multiparametric classification and study of solid tumors.
Influence of KIR Genes and HLA Class I Ligands on Overall and Event-Free Survivals after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Myelogenous Leukemia
Authors: Ekaterina G Khamaganova, Elena N. Parovichnikova, Larisa A. Kuzmina, Sergei M Kulikov, Valeriy G Savchenko
Journal: Blood (2015)
A phase Ib study of lumretuzumab, a glycoengineered monoclonal antibody targeting HER3, in combination with carboplatin and paclitaxel as 1st-line treatment in patients with squamous non-small cell lung cancer
Authors: J.M. Cejalvo, T. Fleitas, E. Felip, A. Navarro Mendivil, M. Martinez-Garcia, A. Taus, N. Leighl, U. Lassen, M. Mau Soerensen, C. Adessi, F. Michielin, W. Jacob, I. James, M. Ceppi, M. Weisser, A. Cervantes
Journal: Annals of Oncology (2016)
TMIC-05. FSTL1, A MARKER FOR PERITUMORAL BRAIN EDEMA AND PROGNOSIS IN GLIOMA
Authors: Yongping You
Journal: Neuro-Oncology (2016)

Follistatin-like 1 (FSTL1), encoding a protein similar to follistatin, belongs to the SPARC (the secreted protein, acidic, rich in cysteine) family. In previous studies, FSTL1 was upregulated in glioblastoma and coexpression of FSTL1 with p53 was associated with poor survival of patients with glioblastoma multiformes (GBM). Here we report that, in glioma, FSTL1 promoted cell proliferation, invasion, migration and peritumoral brain edema (PTEB). It not only activated membrane receptor-DIP2A(disco interacting protein 2 homolog A) but also prevented nuclear translocation of DIP2A by competitive binding to DIP2A. A portion of FSTL1 excreted to extracellular space combined to DIP2A and activated AKT signaling. And the other portion of FSTL1 located in cytoplasm interacted with DIP2A to form a functional complex and prevented nuclear translocation of DIP2A. We also detected that DIP2A was involved in the DMAP1(DNA methyltransferase 1 associated protein 1)-HDAC2(histone deacetylase 2) repressive transcription complex through complexation with DMAP1 in nucleus, and then enhanced transcriptional inhibition of FOS(Fos proto-oncogene, AP-1 transcription factor subunit) by the HDAC2 repressive transcription complex. Cytoplasmic FSTL1 acts as a scaffold to impair the interaction between DIP2A and DMAP1-HDAC2 repressive transcription complex, inhibiting the mRNA transcriptional silencing function of HDAC2 on FOS mRNA. We identified the microRNA miR-198, derived from the 3’-untranslated region of FSTL1 mRNA, as a potential anti-oncogene in glioblastoma. The long noncoding RNA lncRNA-H19 adjusted the switch between miR-198 and FSTL1 through competitive binding to KSRP(KH-type splicing regulatory protein) in glioma. Our data indicated an association of FSTL1 with pathological grade, cell proliferation, invasion, migration and PTBE, suggesting that it is a potential marker for increased malignancy and PTBE in glioma.
An open-label phase II study of intravenous bortezomib and oral panobinostat (LBH589) in adult patients with relapsed/refractory peripheral T-cell lymphoma (PTCL) or NK/T-cell lymphoma (NKL) after failure of conventional chemotherapy.
Authors: D. C. Tan, P. Chan, B. L. Ng, B. K. Yap, Y. H. Chan, L. P. Koh, F. A. Wahid, S. T. Lim, N. S. Chin, W. S. Kim, S. Y. Tan, Y. T. Goh
Journal: Journal of Clinical Oncology (2011)

TPS224 Background: Relapsed/refractory PTCL and NKL after conventional chemotherapy carry an extremely poor prognosis and there is currently no proven treatment available. Panobinostat (PAN), a pan-deacetylase inhibitor targets epigenetic and multiple oncogenic pathways, while bortezomib (BTZ) exerts pleotropic antitumor effects, including the inhibition of the NF-KB pathway, leading to cell apoptosis. Separately, both agents have shown activity in PTCL and NKL. In vitro and in vivo studies have demonstrated potent synergistic cytotoxicity of the combination. Additionally, inhibition of HDAC6 by PAN abrogates BTZ-induced protective aggreosome formation and accentuates BTZ induced endoplasmic reticulum stress, leading to further apoptosis. Collectively, these data provide a strong rationale for the first clinical trial of this combination in PTCL and NKL Methods: This is an open label, phase II multicenter, multinational clinical trial(NCT00901147), with a Gehan’s 2- stage design. Aiming for a response rate of ≥ 25%, 11 patients (pts) will be recruited in stage 1 and a further 12 in stage 2 if ≥1 response is observed at stage 1. Pts will receive oral PAN (20 mg), administered thrice weekly and BTZ (IV 1.3 mg/m2) administered twice weekly, both for 2 of 3 weeks. To be eligible, pts ≥ 21years old with ECOG performance status 0-2 and histologically confirmed PTCL NOS, angioimmunoblastic T-cell lymphoma, extranodal NKL nasal type, enteropathy-type T-cell lymphoma, hepatosplenic T-cell lymphoma or anaplastic large cell lymphoma (ALK-1-negative or ALK 1-positive post-autologous transplant), need to have relapsed or are refractory to at least one systemic therapy. Disease has to be measurable by the IMW criteria. The primary endpoint is the objective response rate and the secondary the points include overall survival, duration of response and safety. Correlative biomarker analysis will be performed. Radiological tumor assessments by CT/PET scans will be performed for evaluation of response after every 2 cycles of therapy. To date, 5 of planned 25 patients have been enrolled.
RARE-49. DEFINING RELAPSE PATTERNS IN PRIMARY CNS DIFFUSE LARGE B-CELL LYMPHOMA: A MULTICENTER STUDY
Authors: Nancy Wang, Camilo Fadul, Melissa Davis, Lakshmi Nayak, Joachim Baehring, Tracy Batchelor
Journal: Neuro-Oncology (2016)

The objective of this study was to describe relapse patterns in patients with primary CNS diffuse large B-cell lymphoma (DLBCL). Primary CNS lymphoma is a rare, malignant extra-nodal lymphoma confined to the brain, spinal cord, leptomeninges, and eyes. It accounts for less than 3% of primary brain tumors; over 90% are histologically DLBCL. Survival is inferior to other forms of extra-nodal DLBCL with relapse rates of > 50%, historically within two years of diagnosis. Post-remission surveillance is currently based on consensus opinion, and a better understanding of relapse patterns is required to determine optimal surveillance. We conducted a retrospective analysis of patients with primary CNS DLBCL seen at three tertiary hospitals. Survival estimates were calculated using the Kaplan-Meier method. A total of 172 immunocompetent patients with primary CNS DLBCL achieved radiographic CR to induction therapy. Median age at diagnosis was 62.6 years, with median Karnofsky Performance Score at diagnosis of 80. Initial treatment consisted of high dose methotrexate-based polychemotherapy in 53.4%, radiation therapy in 13.4% and intrathecal chemotherapy in 10.5%. 14% underwent stem cell transplantation. The relapse rate was 57% at a median interval of 2.9 years from diagnosis. Method of relapse detection was clinical in 49%, radiographic in 39%, and combined in 11.2%. The first relapse occurred at a remote CNS site in the majority of patients (57%). The 2, 5, and 10-year progression-free survival proportions were 74.8%, 45.6%, and 23.8%, respectively. We found that late and systemic relapse were more common than previously reported. Only half of the relapses were detectable clinically by symptoms. These results support current consensus guidelines of clinical and radiographic surveillance up to 10 years after diagnosis.
NIMG-74. A CASE OF NON-CLASSICAL PARANEOPLASTIC ENCEPHALITIS SUPPORTED BY CHANGES ON MRI AND FDG-PET
Authors: David Kamson, Anjali Gera
Journal: Neuro-Oncology (2016)

Here we present a case of definite non-classical paraneoplastic encephalitis with clinical and radiographic (MRI, PET) response after systemic chemotherapy. Our patient was a 67-year-old female with a 50-year history of smoking developing progressive dementia. Her first symptom was memory impairment for which her initial neurologic evaluation was negative, but her MMSE score of 28 yielded the diagnosis of pseudodementia. She was started on citalopram to no avail and subsequently developed hallucinations with paranoid ideation and violent outbursts. She was hospitalized for respiratory distress at a non-affiliated hospital, where her encephalopathy workup revealed absent routine serum paraneoplastic antibody titers, mild CSF pleocytosis with lymphocytic predominance. There was no electrographic evidence of seizures. MRI brain showed serpiginous and nodular cortical T2/FLAIR hyperintense lesions affecting the temporal poles, the right insular and frontal cortex. None of these lesions exhibited contrast-enhancement or restricted diffusion. Three weeks later, she was referred to our institution where repeat MRI revealed new left insular T2/FLAIR involvement yet no new enhancement or diffusion restriction. Brain FDG-PET showed generalized cortical hypometabolism with hypermetabolic areas corresponding to T2/FLAIR lesions. Whole-body PET revealed a hypermetabolic lung mass proven to be SCLC on biopsy. As the brain-imaging pattern was atypical for metastatic disease, paraneoplastic encephalitis was favored and brain irradiation was postponed to evaluate response to systemic treatment. After two cycles of etoposide/cisplatin, agents with poor CNS penetration in the absence of blood-brain barrier breakdown, the patient exhibited modest but significant clinical improvement. Her repeat imaging showed near-complete resolution of insular involvement and marked reduction in the extent of T2/FLAIR cortical hyperintensities without any signs of necrosis. At the same time FDG-PET exhibited reduced number of hypermetabolic lesions and improved generalized cortical metabolism. Our findings perhaps represent imaging evidence of network-wise recovery in the setting of paraneoplastic syndrome treated with systemic chemotherapy.