tbuckley/cabot-search huggingface dataset:
EXTH-47. RAPID CONVERSION OF MUTANT IDH1 FROM DRIVER TO PASSENGER IN A MODEL OF HUMAN GLIOMAGENESIS
Authors: Tor-Christian Aase Johannessen, Joydeep Mukherjee, Pavithra Viswanath, Shigeo Ohba, Sabrina M. Ronen, Rolf Bjerkvig, Russell O. Pieper
Journal: Neuro-Oncology (2016)

Missense mutations in the active site of isocitrate dehydrogenase 1 (IDH1) biologically and diagnostically distinguish low-grade gliomas and secondary glioblastomas from primary glioblastomas. IDH1 mutations lead to the formation of the oncometabolite 2-hydroxyglutarate (2-HG) from the reduction of α-ketoglutarate (α-KG), which in turn facilitates tumorigenesis by modifying DNA and histone methylation as well blocking differentiation processes. While mutant IDH1 expression is thought to drive the gliomagenesis process, the extent to which it remains a viable therapeutic target remains unknown. To address this question we exposed immortalized (p53/pRb-deficient), untransformed human astrocytes to the mutant IDH1 inhibitor AGI-5198 prior to, concomitant with, or at intervals after, introduction of transforming mutant IDH1, then measured effects on 2-HG levels, histone methylation (H3K4me3, H3K9me2, H3K9me3 or H3K27me3) and growth in soft-agar. Addition of AGI-5198 prior to, or concomitant with, introduction of mutant IDH1 blocked all mutant IDH1-driven changes including cellular transformation. Addition at time intervals as short as 4 days following introduction of mutant IDH1 also suppressed 2-HG levels, but had minimal effects on histone methylation, and lost the ability to suppress clonogenicity in a time-dependent manner. Furthermore, in two different models of mutant IDH1-driven gliomagenesis, AGI-5198 exposures that abolished production of 2-HG also failed to decrease histone methylation, adherent cell growth, or anchorage-independent growth in soft-agar over a prolonged period. These studies show although mutant IDH1 expression drives gliomagenesis, mutant IDH1 itself rapidly converts from driver to passenger.
OS1.7 Regulatory RNAs, a missing link in Glioblastoma response to Temozolomide?
Authors: S. Fritah, W. Jiang, A. Muller, R. Mitra, M. Dieterle, A. Golebiewska, E. Van Dyck, Z. Zhao, F. Azuaje, S. Niclou
Journal: Neuro-Oncology (2016)
CHOP Every 14 Days in Naïve Patients with Diffuse B-Large Cell Lymphoma.
Authors: Araceli Rubio-Martinez, Luis Palomera, Nicolas Gonzalez, Jose A. Domingo, Carlos Arguinano, Fernando Puente, Matilde Perella, Jose A. Angos, Ignacio Sancho, Pilar Herrera, Valle Recasens, Pilar Giraldo
Journal: Blood (2006)
P05.04 Morphine pretreatment improves the therapeutic efficacy of doxorubicin in an orthotopic model of human glioblastoma
Authors: M. Da Ros
Journal: Neuro-Oncology (2016)

The blood-brain barrier (BBB) is a protective mechanism designed to prevent toxins, both endogenous and exogenous, from damaging the Central Nervous System.In protecting the brain, however, the BBB also serves to prevent therapeutic drugs from entering, thus hampering efficacy.High expression levels of ATP binding cassette (ABC) transporters, P-glycoprotein (Pgp), MRP1 and Breast Cancer Resistant Protein (BCRP), at the brain capillary endothelium suggest they play a major role in preventing drug uptake in the brain.In particular, P-gp exhibits a broad substrate specificity interacting with a wide range of molecules, as doxorubicin (Dox) and morphine.We investigated the influence of morphine on the cellular uptake of Dox by parental and P-gp transfected MDCKII cells as in vitro BBB model.Parental and P-gp transfected MDCKII cells were seeded on 6-well plates two days before the experiments.Culture medium was removed; cells were washed twice with PBS and then pre-incubated in Opti MEM medium for 15 min at 37°.After pre-incubation, morphine and Dox, suitable for fluorescence, were added at the final concentration of 20µM and 0,5 µg/mL, respectively.Drug uptake was allowed for 2h at 37° on dark and arrested by prompt cooling on ice and removal of medium.Dox fluorescence was determined in 8,000 events for each sample by using a FACScan flow cytometer, equipped with a 15-mW argon-ion laser for excitation.The data showed Dox accumulation in MDCKII parental cells, without statistically significant difference between Dox and Dox plus morphine groups.The Dox level was significantly increased comparing control group (4.88) vs Dox group (24.4,P<0.01) and Dox plus morphine group (19.82,P<0.05).Conversely, fluorescence data on MDCKII P-gp cells indicated no Dox accumulation in both control and Dox groups.Dox amount increased in MDCKII P-gp cells when administered in presence of morphine.The Dox level was significantly higher comparing control (3.84) vs Dox plus morphine group (12.29,P<0.05).Our results showed a similar uptake of Dox, with or without morphine, in MDCKII parental cells and revealed that MDCKII P-gp cells, treated with Dox plus morphine, presented higher amount of intracellular Dox.Morphine seems to regulate the delivery of Dox through functional inhibition of P-gp on BBB.
Identification of Patients With Stable Chest Pain Deriving Minimal Value From Noninvasive Testing
Authors: Christopher B. Fordyce, Pamela S. Douglas, Rhonda S. Roberts, Udo Hoffmann, Hussein R. Al-Khalidi, Manesh R. Patel, Christopher B. Granger, John Kostis, Daniel B. Mark, Kerry L. Lee, James E. Udelson
Journal: JAMA Cardiology (2017)

Guidelines recommend noninvasive testing for patients with stable chest pain, although many subsequently have normal test results and no adverse clinical events.To describe a risk tool developed to use only pretest clinical data to identify patients with chest pain with normal coronary arteries and no clinical events during follow-up (minimal-risk cohort).This secondary analysis of a randomized, pragmatic comparative effectiveness trial (Prospective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]) includes stable, symptomatic outpatients without known coronary artery disease referred for noninvasive testing at 193 sites in North America.Patients were randomized to receive coronary computed tomography angiography (CCTA) vs functional testing.A low-risk tool was developed and internally validated from July 27, 2010, to September 19, 2013, in 4631 patients receiving CCTA as their initial test, with a median follow-up of 25 months. Logistic regression analysis was used to evaluate pretest variables to determine factors associated with minimal risk using a two-thirds random sample for model derivation (n = 3087) and a one-third sample for testing and validation (n = 1544). The model was then applied to the CCTA and functional testing arms, and test results and event rates were ascertained.A total of 1243 of 4631 patients (26.8%) were in the minimal-risk cohort. The final minimal-risk model included 10 clinical variables that together were correlated with normal CCTA results and no clinical events (C statistic = 0.725 for the derivation and validation subsets; 95% CI, 0.705-0.746): younger age; female sex; racial or ethnic minority; no history of hypertension, diabetes, or dyslipidemia; family history of premature coronary artery disease; never smoking; symptoms unrelated to physical or mental stress; and higher high-density lipoprotein cholesterol level. Across the entire PROMISE cohort, this model was associated with the lowest rates of severely abnormal test results (1.3% for CCTA; 5.6% for functional) and cardiovascular death or myocardial infarction (0.5% for a median of 25 months) among patients at the highest probability (10th decile) of minimal risk.In contemporary practice, more than 25% of patients with stable chest pain referred for noninvasive testing will have normal coronary arteries and no long-term clinical events. A clinical tool using readily available pretest variables discriminates such minimal-risk patients, for whom deferred testing may be considered.clinicaltrials.gov Identifier: NCT01174550.
JaNEO – A phase Ib/II study assessing the neo-adjuvant combination therapy of vinflunine (VFL) with cisplatin (CDDP) followed by radical cystectomy (RC) in patients with muscle-invasive bladder cancer (MIBC)
Authors: A. Hegele, C.-H. Ohlmann, H. Rexer, G. Gakis
Journal: Annals of Oncology (2016)
ENDURANCE-4: Efficacy and Safety of ABT-493/ABT-530 Treatment in Patients with Chronic HCV Genotype 4, 5, or 6 Infection
Authors: Tarik Asselah, Christophe Hezode, Neddie Zadeikis, Magdy Elkhashab, Massimo Colombo, Rui T Marinho, Kosh Agarwal, Frederik Nevens, Ran Liu, Teresa Ng, Federico Mensa
Journal: Hepatology (2016)
Individually Tailored Prophylaxis Using a Risk Score for the Management of Pregnant Women with Increased Risk of Venous Thromboembolism
Authors: Yesim G. Dargaud, Lucia Rugeri, Chloe Fleury, Helene Desmurs Clavel, Jacques Ninet, Catherine Battie, Pascal Gaucherand, Cyril Huissoud, Rene Charles Rudigoz, Christine Trzeciak
Journal: Blood (2015)
Absence of Spred, a Negative Regulator of Tyrosine Kinase Activity, in Acute Myeloid Leukemia Patients
Authors: Valentina Rosso, Cristina Panuzzo, Enrico Bracco, Sonia Carturan, Valentina Campia, Alessandra Favole, Elisabetta Signorino, Pimjai Niparuk, Chiara Calabrese, Luciana De Luca, Antonella Caivano, Annalisa Morano, Francesco Frassoni, Giuseppe Saglio, Daniela Cilloni
Journal: Blood (2012)
P18.02 Comparing quality of glioblastoma resections between care teams
Authors: D. M. J. Müller, P. A. J. Robe, F. Barkhof, W. P. Vandertop, P. C. de Witt Hamer
Journal: Neuro-Oncology (2016)

Background: The extent of resection is important to improve survival in patients with a glioblastoma. The neurosurgeon's aim is to maximize the extent of resection, while preserving functional integrity. A standard to assess and compare the quality of neurosurgical care of teams is lacking. In this study we present a novel volumetric method to quantify resection residues throughout the brain for patient populations. This allows direct comparison of surgical results between care teams. Materials and Methods: All adults with a newly-diagnosed glioblastoma who had neurosurgical treatment in 2012 or 2013 in each of two tertiary referral centres for neuro-oncological care were included in this study. From each of these patient populations the outlines of preoperative tumors and postoperative residues were segmented on MRI. Tumor and residue segmentations were registered to standard space. Brain maps of tumor and residue locations were constructed for each center. Differences between these brain maps were analyzed to explore patient selection and treatment variation. Results: The study cohort consisted of 268 patients who received neurosurgery; 99 were treated by one care team, 169 by the other. Biopsies were performed in 88 patients and resective surgery in 180. The tumor localization maps confirmed established preferential locations of glioblastoma. A significant dissimilarity was noted as the patient populations of the care teams differed in tumor distribution, which may indicate differential patient referral, selection or recruitment. For patients who had resective surgery, the resection probability maps demonstrated significant differences in resected regions in the anterior internal capsule and the caudate nucleus, which may indicate treatment variation. Several arguments for these differences were considered by the care teams. Further analysis will explore whether these variations are associated with differential functional outcome or survival. Conclusions: Brain maps of tumor localization convey important information that can be used to compare neurosurgical centers in terms of patient selection. In addition, dissimilar resection probability maps may indicate treatment variations. This novel volumetric approach can provide objective arguments for discussions between care teams on the quality of neurosurgical care for patients with a glioblastoma.
Histone Deacetylase Inhibitors Induce Cell Growth Inhibition and Apoptosis in NPM1-Mutated AML Cells: A Possible Role for Epigenetic Therapies in AML Carrying NPM1 Gene Mutations
Authors: Ilaria Gionfriddo, Federica Mezzasoma, Federica Cecchetti, Roberta Rossi, Francesca Strozzini, Francesco Di Raimondo, Valentina Pettirossi, Brunangelo Falini, Maria Paola Martelli
Journal: Blood (2011)
Evaluation of neoadjuvant weekly nanoparticle albumin-bound paclitaxel for HER2-negative breast cancer
Authors: A. Nagayama, A. Matsui, A. Tachibana, N. Suzuki, M. Hirata, Y. Oishi, Y. Hamaguchi, Y. Murata, Y. Okamoto
Journal: Annals of Oncology (2016)
P10.03 The prognostic role of primary treatment in pediatric High-Grade Gliomas: the experience at Meyer Children’s Hospital
Authors: M. Lucchesi, S. Scoccianti, M. Guidi, L. Facchini, S. Farina, C. Fonte, C. Favre, L. Genitori, I. Sardi
Journal: Neuro-Oncology (2016)
IL15 Enhances Proliferation and Effector Function of Antigen-Specific Cytotoxic T Lymphocytes (CTLs) and Mitigates the Suppressive Action of Regulatory T Cells (Tregs).
Authors: Serena Kimi Perna, Biagio De Angelis, Daria Pagliara, Lan Zhan, Cliona M Rooney, Helen E. Heslop, Malcolm K Brenner, Gianpietro Dotti, Barbara Savoldo
Journal: Blood (2009)
Mouse genomic screen reveals novel host regulator of metastasis
Authors: Toni Celià-Terrassa, Yibin Kang
Journal: Genome biology (2017)

Tumor cells have to overcome challenges in the host tissue microenvironment to metastasize successfully to distant organs. In a recent Nature study, a genome-wide functional screen demonstrated that deficiency of the sphingosine-1-phoshate (S1P) transporter gene Spns2 in endothelium increased immune-mediated cell killing by T cells and natural killer (NK) cells, thereby suppressing metastatic colonization.
Aberrant Activation of the PI3K/mTOR Pathway Promotes Resistance to Sorafenib in AML
Authors: Oscar Lindblad, Eugenio Cordero, Alexandre Puissant, Lucy Macaulay, Nuzhat N. Kabir, Jianmin Sun, Karin Haraldsson, Åke Borg, Fredrik Levander, Kimberly Stegmaier, Kristian Pietras, Lars Ronnstrand, Julhash U. Kazi
Journal: Blood (2015)
Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases
Authors: Holly A F Stessman, Bo Xiong, Bradley P Coe, Tianyun Wang, Kendra Hoekzema, Michaela Fenckova, Malin Kvarnung, Jennifer Gerdts, Sandy Trinh, Nele Cosemans, Laura Vives, Janice Lin, Tychele N Turner, Gijs Santen, Claudia Ruivenkamp, Marjolein Kriek, Arie van Haeringen, Emmelien Aten, Kathryn Friend, Jan Liebelt, Christopher Barnett, Eric Haan, Marie Shaw, Jozef Gecz, Britt-Marie Anderlid, Ann Nordgren, Anna Lindstrand, Charles Schwartz, R Frank Kooy, Geert Vandeweyer, Celine Helsmoortel, Corrado Romano, Antonino Alberti, Mirella Vinci, Emanuela Avola, Stefania Giusto, Eric Courchesne, Tiziano Pramparo, Karen Pierce, Srinivasa Nalabolu, David G Amaral, Ingrid E Scheffer, Martin B Delatycki, Paul J Lockhart, Fereydoun Hormozdiari, Benjamin Harich, Anna Castells-Nobau, Kun Xia, Hilde Peeters, Magnus Nordenskjöld, Annette Schenck, Raphael A Bernier, Evan E Eichler
Journal: Nature Genetics (2017)
Phenotypical, Functional and Genetic Characterization of Mesenchymal Stem Cells Derived from the Spleen of Patients with Myelofibrosis
Authors: Maria Antonietta Avanzini, Vittorio Abbonante, Melissa Mantelli, Valentina Poletto, Adele Aronica, Daniela Ingo, Antonia Moretta, Gloria Acquafredda, Elisa Bonetti, Paolo Catarsi, Margherita Massa, Rita Campanelli, Gabriela Fois, Laura Villani, Christian A Di Buduo, Lorenzo Cobianchi, Marco Zecca, Rita Maccario, Giovanni Barosi, Alessandra Balduini, Vittorio Rosti
Journal: Blood (2014)
Efficacy and safety of the combination of bevacizumab (BEV) and temsirolimus (TEM) in patients with metastatic renal cancer (mRCC) after first-line anti-VEGF treatment: A Hellenic Cooperative Oncology group (HeCOG) phase II trial
Authors: K. Koutsoukos, F. Zagouri, K. Tzannis, V. Karavasilis, E. Samantas, G. Aravantinos, A. Koutras, I. Gkerzelis, E. Chamylos, E. Kostouros, M. Lykka, G. Tsironis, I. Dimitriadis, M. Liontos, G. Fountzilas, M. Dimopoulos, A. Bamias
Journal: Annals of Oncology (2016)
The CHIVA study: a GINECO randomized double blind phase II trial of nintedanib versus placebo with the neo-adjuvant chemotherapy (NACT) strategy for patients (pts) with advanced unresectable ovarian cancer (OC). Report of the interval debulking surgery (IDS) safety outcome
Authors: G. Ferron, G. De Rauglaudre, I.L. Ray-Coquard, A. Lesoin, F. Joly, A. Lortholary, N. Raban, J. Peron, E. Malaurie-Agostini, S. Gouy, M.-C. Kaminsky, J. Meunier, J. Alexandre, D. Berton-Rigaud, F. Coussy, L. Favier, L. Venat-Bouvet, F. Marmion, P. Combe, E. Pujade-Lauraine
Journal: Annals of Oncology (2016)
Phase 2 study of ceritinib in ALKi-naïve patients (pts) with ALK-rearranged (ALK+) non-small cell lung cancer (NSCLC): Whole body responses in the overall pt group and in pts with baseline brain metastases (BM)
Authors: E. Felip, S. Orlov, K. Park, C.-J. Yu, C.-M. Tsai, M. Nishio, M.C. Dols, M. McKeage, W.-C. Su, T.S.K. Mok, G. Scagliotti, D.R. Spigel, V.Q. Passos, V. Chen, F. Munarini, A. Shaw
Journal: Annals of Oncology (2016)
MPTH-18. COMPREHENSIVE MUTATIONAL AND CYTOGENETIC ANALYSIS REVEALED GENETIC PROGNOSTIC FACTORS IN GRADE II AND III GLIOMAS
Authors: Kosuke Aoki, Hiromichi Suzuki, Hideo Nakamura, Keitaro Matsuo, Kazuya Motomura, Fumiharu Ohka, Masahiro Mizoguchi, Yasutomo Momii, Yoshihiro Muragaki, Reiko Watanabe, Ichiro Ito, Toshihiko Wakabayashi, Seishi Ogawa, Seishi Ogawa, Atsushi Natsume
Journal: Neuro-Oncology (2016)

WHO grade II and III gliomas (lower-grade gliomas, LGGs) are usually slowly progressive but rarely curable brain caners. Recently, we have delineated a comprehensive picture of genetic alterations in LGGs and revealed that they could be clearly classified into three genetic subtypes characterized by distinct genetic and clinical features: IDH1/2 mutated tumors with 1p/19q co-deletion (Type−I), IDH1/2 mutated tumors without 1p/19q co-deletion (Type−II) and IDH1/2wild-type tumors (Type−III). Each genetic subtype shows substantially different overall survival (OS). In the current study, we analyzed a large data set of patients with LGGs fully genotyped for major genetic lesions to determine the prognostic significance of additional genetic alterations. We analyzed genetic alterations detected by exome and/or targeted sequencing as well as SNP-array karyotyping obtained from clinically well-annotated 724 patients with LGGs from the Japan and The Cancer Genome Atlas cohorts. We performed univariate and multivariate Cox hazard proportional analyses for OS; multivariate models incorporated age at the time of surgery (≥60 vs. <60 year-old), WHO grade, and extent of resection with stratification of cohorts. In the multivariate Cox regression analysis, we revealed that several genetic alterations have subtype-specific prognostic significance: NOTCH1 mutation in Type-I, high-level focal amplification of CDK4, PIK3R1 mutation, and loss of chromosome 9p in Type-II, and loss of chromosome 10 in Type-III tumors. Except for NOTCH1mutations, these alterations are frequently affected in glioblastomas, suggesting their link to glioblastoma pathophysiology. In Type-III tumors, WHO grade was the strongest predictor of OS; WHO grade II tumors, especially those without loss of chromosome 10, showed a substantially better OS than other Type-III tumors with grade III histology or loss of chromosome 10. Subtype-specific genetic lesions can be used to further stratify patients for OS to improve management of LGGs.
Erratum: A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer (Clinical Cancer Research (2000) 6 (798-806))
Authors: I. Ganly, S. G. Eckhardt, G. I. Rodriguez, D. S. Soutar, Randal A Otto, A. G. Robertson, O. Park, M. L. Gulley, C. Heise, D. D. Von Hoff, S. B. Kaye
Journal: Clinical Cancer Research (2000)
Rate of Inhibitor Development in Hemophilia A Patients Treated with Plasma Derived or Recombinant Factor VIII Concentrates. A Systematic Review of the Literature.
Authors: Alfonso Iorio, Susan Halimeh, Christoph Bidlingmaier, Leonardo R. Brandao, Carmen Escuriola-Ettingshausen, Neil A Goldenberg, Alessandro Gringeri, Susanne Holzhauer, Gili Kenet, Ralf Knoefler, Wolfhart Kreuz, Karin Kurnik, Daniela Manner, Emanuela Marchesini, Maura Marcucci, Elena Santagostino, Guy Young, Pier Mannuccio Mannucci, Ulrike Nowak-Gottl
Journal: Blood (2009)
Residual Disease on FDG-PET and Multiple Lines of Prior Therapy Predict Poorer Outcomes Following Autologous Hematopoietic Stem Cell Transplantation for Lymphoma
Authors: Robert N Lown, Anastasia Constantinidou, Caroline Ebdon, Kabir Mohammed, Mark Ethell, Ian Chau, David Cunningham, Michael Potter, Bhupinder Sharma
Journal: Blood (2014)
RARE-61. CLINICAL, RADIOLOGIC, AND PATHOLOGIC REVIEW OF ASTROBLASTOMA: THE MD ANDERSON EXPERIENCE
Authors: Rebecca A. Harrison, Joo Yeon Nam, Gregory N. Fuller, Jason M. Johnson, Barbara J. O’Brien
Journal: Neuro-Oncology (2016)

Astroblastoma is an uncommon and controversial glioma. Due to its rarity, there remains a lack of consensus regarding its diagnostic features, clinical course, and optimal management. The recent revised WHO Classification of Tumours of the Central Nervous System (2016) reaffirmed the codification of astroblastoma as a distinct nosologic entity. This renewed acknowledgement of astroblastoma underscores the need to better understand this tumor and its clinical and paraclinical features. We searched the MD Anderson Cancer Center pathology database for cases of astroblastoma, and performed a retrospective chart review for pediatric and adult cases diagnosed between 2004 and 2015. All diagnoses were confirmed by the pathology collaborator. We classified the cases as follows: typical astroblastoma pathology, astroblastoma with anaplastic features, and pediatric astroblastoma (<18 years old). Clinical, radiologic, and pathologic information was obtained from chart review and data was summarized using descriptive statistics. We identified 12 patients with a diagnosis of astroblastoma: 8 adult and 4 pediatric cases. Follow-up interval from diagnosis ranged from 4 months to 11 years. All tumors were supratentorial, with no predilection for a particular lobe. Half of the adult and pediatric cases had pathologic features designated as anaplastic, with evidence of vascular proliferation and/or necrosis. All lesions demonstrated MR contrast enhancement and appeared well-circumscribed. One pediatric case had tumor progression during follow up, while 2 of the 4 adults with anaplastic features and 3 of 4 of those with typical pathology had progression. This case series describes the clinical, radiographic, and pathologic features seen with astroblastoma, contributing to our knowledge on this rare tumor and potentially facilitating diagnosis. Continued efforts to publish these cases will further our understanding of this unique tumor entity. Longer follow up is needed to better delineate the clinical course of these patients.
The Role of Oxidative Stress on Telomere Shortening, Telomere Dysfunction and Damage to Telomere G- Strand Overhang - A Putative Model of Carcinogenesis in Fanconi Anemia Cells.
Authors: Meir Lahav, Orit Uziel, Hagai Reshef, Anat Ravid, Ina Fabian
Journal: Blood (2005)
Phase II Trial of 90y-Ibritumomab Tiuxetan Treatment as Consolidation After 6th R-CHOP Chemotherapy in Patients with Limited-Stage, Bulky Diffuse Large B Cell Lymphoma.
Authors: Deok-Hwan Yang, Won Seog Kim, Cheolwon Suh, Jae-Yong Kwak, Joo-Sep Jung, Sung Hyun Kim, Jin Seok Kim, Je-Jung Lee, Hyeoung-Joon Kim
Journal: Blood (2009)