tbuckley/cabot-search huggingface dataset:
PDTB-13. DETECTION OF HISTONE H3 MUTATIONS IN PEDIATRIC GLIOMA VIA TUMOR DNA DERIVED FROM CEREBROSPINAL FLUID
Authors: Amanda Saratsis, Tina Huang, Andrea Piunti, Rishi Lulla, Tadanori Tomita, C. David James, Ali Shilatifard
Journal: Neuro-Oncology (2016)

Pediatric high-grade gliomas, including glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG), are highly morbid tumors that are biologically distinct from their adult counterparts. Specifically, genomic analyses of pediatric gliomas reveal unique somatic missense mutations in genes encoding histone H3 variants H3.3 (H3F3A) and H3.1 (HIST1H3B). These gain-of-function mutations result in replacement of lysine 27 with methionine (K27M), or glycine 34 with valine or arginine (G34V/R). Since these mutations are distinct to tumor location and prognosis, they may serve as biomarkers for diagnosis and monitoring response to treatment. Previous studies show cerebrospinal fluid (CSF) is enriched for cell-free and tumor DNA shed by brain tumor cells. Here, we describe a method to isolate DNA in CSF from children with brain tumors to detect K27M or G34V mutations, without the need for tumor tissue acquisition. Ventricular CSF was obtained from children harboring brain tumors via CSF diversion devices (n=9). Linear polyacrylamide was used to precipitate cfDNA fragments larger than 20 base pairs from CSF. Two strategies were employed to detect Histone H3 K27M and G34V mutations: global characterization of genomic aberrations with Sanger sequencing, and targeted detection of mutations via PCR with specially designed primers. Immunohistochemistry and Sanger sequencing was employed to validate CSF analysis results in matched tumor tissue specimens. H3K27M and H3G34V mutations were detected in CSF containing as low as 1ng cfDNA per microliter (n=2). Results were validated via mutation profiling of tumor tissue from the same patients. No mutation was detected in DNA extracted from negative controls (n=7). Histone H3 K27M and G34V mutations are detectable in DNA extracted from CSF of pediatric high-grade glioma patients. Our findings suggest the feasibility of “liquid biopsy” to facilitate or complement tissue diagnosis, which may prove valuable for stratification to targeted therapies and monitoring treatment response.
The clinical outcome of pazopanib treatment for soft tissue sarcomas: A Japanese Musculoskeletal Oncology Group study
Authors: Akihiko Matsumine, Tomoki Nakamura, Akira Kawai, Nobuhito Araki, Takahiro Goto, Tsukasa Yonemoto, Hideshi Sugiura, Yoshihiro Nishida, Hiroaki Hiraga, Takafumi Ueda
Journal: Annals of Oncology (2016)
Prognostic factors in men with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide (ENZA) or bicalutamide (BIC) in TERRAIN
Authors: A. Heidenreich, N. Shore, A. Villers, L. Klotz, D.R. Siemens, S. van Os, B. Baron, F. Wang, S. Chowdhury
Journal: Annals of Oncology (2016)
Post-Ebola reforms deserve support
Authors: Margaret F C Chan
Journal: BMJ (2017)

We agree with Moon and colleagues1—most of the 11 000 Ebola deaths in west Africa could have been prevented had the world been much better prepared. Those three countries had broken health systems, rudimentary capacities for research and logistics, and no early warning systems. People put their trust in traditional healers. Clinicians had unsafe treatment centres, no vaccines or treatments, …
Non pegylated liposomal doxorubicin (npld, myocettm) + carboplatin (cb) in patients (pts) with ovarian cancer in late relapse (oclr): a phase 2 gineco study
Authors: B. You, F. Joly, I.L. Ray-Coquard, C. El Kouri, A. Mercier-Blas, D. Berton-Rigaud, E. Kalbacher, O. Cojocarasu, M. Fabbro, J. Cretin, A. Zannetti, S. Abadie-Lacourtoisie, D. Mollon, A.-C. Hardy-Bessard, M. Provansal, G. Freyer
Journal: Annals of Oncology (2016)
Outcome Prediction in CLL Patients Based on a Disease-Specific Oligonucleotide Microarray.
Authors: A. Rodriguez, R. Villuendas, P. de la Cueva, E. Gomez, N. Hernandez, J. Garcia-Marco, L. Yañez, M.A. Cuadrado, E. Conde, F. Cifuentes, M. Pollan, M.A. Piris
Journal: Blood (2005)
Pantoprazole affecting docetaxel resistance pathways via autophagy (PANDORA): A phase II trial in men with metastatic castrate resistant prostate cancer (mCRPC)
Authors: A. Hansen, I. Tannock, A.J. Templeton, A. Prawira, J. Knox, F. Vera-Badillo, E. Chen, M.B. Zavitz, L. Wang, A. Evans, Q. Tan, B. Wouters, S. Sridhar, A. Joshua
Journal: Annals of Oncology (2016)
A phase I, open-label, study of GSK2879552, a lysine-specific demethylase 1 (LSD1) inhibitor, in patients with relapsed/refractory small cell lung carcinoma (SCLC)
Authors: V. Moreno, T.M. Bauer, J. Infante, R. Govindan, B. Besse, E. Bertino, A. Martinez Marti, T. Piontek, A. Dhar
Journal: Annals of Oncology (2016)
Risk of pulmonary embolism and deep venous thrombosis in patients with asthma: a nationwide case−control study from Sweden
Authors: Bengt Zöller, Mirnabi Pirouzifard, Ashfaque A. Memon, Jan Sundquist, Kristina Sundquist
Journal: European Respiratory Journal (2017)

Asthma is associated with an increased risk of pulmonary embolism (PE) but little is known about whether asthma is associated with an increased risk of deep venous thrombosis (DVT). The aim in this study was to determine the risk of the first event of PE, DVT or a combination of PE and DVT in patients with asthma.We conducted this nationwide case-control study using data from Swedish nationwide registries. We included 114 366 Swedish-born patients with a first hospital diagnosis of PE, 76 494 patients with DVT and 6854 patients with both PE and DVT in Sweden between 1981 and 2010. We also included five age-, sex- and education-matched population controls. All previous hospital diagnoses of asthma were identified. Conditional logistic regression was used to compute odds ratios with adjustment for potential confounders.Asthma was associated with an adjusted odds ratio for PE of 1.43 (95% CI 1.37-1.50), for DVT of 1.56 (95% CI 1.47-1.65) and for combined PE and DVT of 1.60 (95% CI 1.32-1.93). Asthma was associated with an increased risk of PE, DVT and combined PE and DVT.Thus, the inflammation conferred by asthma seems to have systemic (and not just local) prothrombotic effects with increased risk of both DVT and PE.
An Interim Report Experience on Acute Leukemia and High Dose Therapy in Jehovah’s Witnesses Treated in a Single Institution.
Authors: Patrizio P. Mazza, Giulia G. Palazzo, Barbara B. Amurri, Giovanni G. Pisapia, Giancarla G. Pricolo, Antonella A. Prudenzano, Loredana L. Stani
Journal: Blood (2004)
CSIG-01. CASEIN KINASE 2 IS A MAJOR REGULATOR OF MEDULLOBLASTOMA GROWTH AND METASTASIS
Authors: Gordon Li, Gigi Nwagbo
Journal: Neuro-Oncology (2016)

Medulloblastoma (MB) is the most common malignant pediatric brain tumor. While surgery, craniospinal irradiation, and chemotherapy have resulted in a cure rate of 70%, the surviving patients are afflicted with neurocognitive impairment, endocrine dysfunction, and a severe decrease in quality of life. Consequently, better and more effective treatments are needed to treat these young patients. Casein kinase 2 (CK2) is a highly conserved pleiotropic serine/threonine kinase that has been associated with cell survival in many cancers including adult brain tumors. CK2 is an intriguing therapeutic target for solid tumors and a phase I/II clinical trial testing the safety and tolerability of the CK2 inhibitor CX-4945 is now underway. Our findings demonstrate that CK2 plays an integral role in MB tumorigenesis and metastasis. We have discovered that the CK2 isoform, CK2a, has increased expression in all MB molecular subgroups. Also MB patients with elevated CK2a expression have a significantly worse prognosis. To determine if CK2 plays an important role in MB tumorigenesis we generated MB cell lines with modulated CK2 isoform (CK2a or CK2b) expression. We discovered that exogenous expression of CK2a, increased MB cell growth ~3-fold, while CK2b expression increased growth ~2-fold. Consistently, treatment with different CK2 inhibitors (CX-4945, TBB, TBBz) decreased MB cell growth 2- to 3-fold. We expanded our analysis to MB metastasis and discovered that CK2 can regulate MB cell migration and invasion. Lastly, we screened 4,000 FDA approved compounds to identify molecules that work synergistically with CX-4945 to reduce MB cell growth. We discovered that temozolomide (TMZ), which is part of the standard of care for adult brain tumors, reduced MB growth an additional 40% over CX-4945 treatment alone. Our data suggests that CK2 regulates MB tumorigenesis and metastasis, and inhibition of CK2 with CX-4945 is a promising new MB therapeutic.
Use of complementary and alternative medicine and spiritual practices among women with ovarian carcinoma in the southeastern United States
Authors: W. A. Spannuth, J. M. Estes, L. Powell, J. M. Straughn., E. E. Partridge, G. P. Parham
Journal: Journal of Clinical Oncology (2006)

15048 Background: The use of complementary and alternative medicine (CAM) among women with gynecologic malignancies has been described in a number of studies from the Midwestern and Western United States. There is limited data on the use of CAM in women with gynecologic malignancies in the Southeastern United States. Therefore, we sought to evaluate the use of CAM and spiritual practices among women with ovarian carcinoma in the Southeastern United States. Methods: Women with the diagnosis of ovarian carcinoma undergoing chemotherapy were recruited from the gynecologic oncology clinic. Patients underwent a face-to-face interview by a research assistant regarding their use of CAM as well as their spiritual practices. Results: 39 women participated in the interview. 26 patients (67%) had used CAM since being diagnosed with cancer. CAM use was not affected by age, annual income, or number of treatments. The majority of women who used CAM had a college education or higher (69%). The most frequently used CAM therapies included mind-body techniques (44%), herbal therapy (38%), and dietary supplements (28%). The most common mind-body technique was music therapy (28%) followed by meditation (21%). The most common dietary supplement used was fish oil, and the most common herbal therapy was green tea (77%). 28% of patients had used an alternative health care provider, most commonly a chiropractor (13%). The most common reason for using CAM was relief of side-effects from treatment (28%). All patients reported some use of spiritual practices. 95% of patients pray with 90% having asked others to pray for their health. 82% had spoken to a religious figure and 26% had a religious sacrament performed for their health. 87% of patients would like their physician to pray with them. Conclusion: Patients with ovarian cancer in the Southeastern United States frequently use CAM including mind-body techniques, herbal therapy, and dietary supplements. The majority of patients believe that spirituality is an important aspect of their cancer therapy. Physicians should be aware of the number of patients who incorporate CAM and spirituality into their standard therapy. No significant financial relationships to disclose.
GENT-06. IN VIVO EXPRESSION OF MUTATED IDH1 (R132H) GENE IN A MOUSE MODEL OF YOUNG ADULT GLIOBLASTOMA HAS IMPACT IN MEDIAN SURVIVAL, DNA-REPAIR PATHWAYS, AUTOPHAGY AND OLIGODENDROCYTE DIFFERENTIATION
Authors: Felipe J Nunez, Flor M Mendez, Carl Koschmann, Alexandra Calinescu, Meghna Saxena, Padma Kadiyala, Marsha Savelieff, Rohin Patel, Shaan Manawar, Sriram Venneti, Marta Dzaman, Pedro R Lowenstein, Maria G Castro
Journal: Neuro-Oncology (2016)

Glioblastoma Multiforme (GBM) is a malignant primary brain tumor. Genomic analysis of GBMs revealed somatic mutations associated with particular subtypes. Young adult GBMs harbor mutations in Isocitrate Dehydrogenase 1 (IDH1-R132H), a metabolic gene, and epigenetic regulators, ATRX and H3.3G34. IDH1-R132H is a gain of function mutation and generates a new metabolite 2-hydroxglutarate (2HG) which leads to alterations in histone methylation patterns. To evaluate the role of these mutations in GBM development, we developed an in vivo model of young adult GBM harboring IDH1-R132H, P53 knockdown and ATRX knockdown in neonatal mouse brain using the Sleeping Beauty Transposase system. Through this model we uncovered the impact of genetic lesions, histone methylation, DNA-repair mechanisms, autophagy and oligodendrocyte differentiation in tumor development. Tumors were induced by injecting NRAS and shP53 plasmids in the lateral ventricle of C57BL/6 neonatal mice with or without IDH1-R132H, or shATRX. The delivery of the plasmids and tumor development was monitored by in vivoimaging. Moribund animals were perfused and analyzed by immunocytochemistry. We also generated GBM neurospheres (NS) for molecular analysis. IDH1-R132H expression increased the levels of histone methylation and increased median survival (MS > 160 DPI) compared with control groups: NRAS/shP53 (MS=90 DPI) and NRAS/shP53/shATRX (MS = 72 DPI). ϒH2AX expression after radiation treatment demonstrated increased levels of DNA-repair. Also, there is increased expression of autophagy-related proteins (Atg) in IDH1-R132H NS. Finally IDH1-R132H tumors expressed oligodendrocyte progenitor cells markers (NG2, PDFGRa) but did not express oligodendrocyte differentiation markers (MBP) by immunohistochemistry. In conclusion, genetically engineered mice harboring IDH1-R132H in combination with ATRX knockdown displayed phenotypic features of young adult GBM, with increased MS. This could be attributed to increased DNA-repair, genomic stability, and autophagy mechanisms which could be used to develop novel therapeutic strategies. Work supported by NIH/NINDS and Leah’s Happy Heart and Chad Tough Foundations.
The Impact of Therapeutic Management and Prognostic Factors on the Outcome of Primary Cutaneous B-Cell Lymphomas (PCBCL) (IELSG 11 Study)
Authors: Sergio Cortelazzo, Michael Mian, Maria Cantonetti, Andreas Sarris, Andrea Rossi, Alessandro Rambaldi, Giuseppe Lombardo, Felice Pasini, Achille Ambrosetti, Liliana Devizzi, Mario Busetto, Osnat Bairey, Emilio Berti, Giovanni Martinelli, Richard Tsang, Silvia Rudoy, Robert Blum, Andres JM Ferreri, Graziella Pinotti, Enrico Pogliani, Emanuele Zucca
Journal: Blood (2008)
GENT-34. EPIGENOMIC STEMNESS SIGNATURE ASSOCIATED WITH GLIOMA MOLECULAR SUBTYPES
Authors: Tathiane Malta, Maciej Wiznerowicz, Houtan Noushmehr
Journal: Neuro-Oncology (2016)

Despite the past significant progress, glioma field faces suboptimal disease classification which impact patient management and treatment. Recent study about genomic and epigenomic landscape of gliomas showed a distinct subtype of IDH-mutant, named G-CIMP-low, with loss of DNA methylation at SOX-family binding sites in intergenic regions, and overexpression of cell cycle genes, suggesting a stem cell phenotype. This subgroup was associated with poor survival. Alongside, a stem cell-like phenotype in various cancer is directly correlated with increased aggressiveness. We hypothesize that a stem cell signature can identify subtypes of glioma associated with poor outcome and improve our comprehension of glioma biology and classification. We analysed molecular profiles from 686 TCGA gliomas (532 LGG; 154 GBM) in order to score the features of tissue de-differentiation. We derived metrics to measure undifferentiated states in tumor samples to identify glioma samples with cancer stem cell phenotype. We observed that gliomas with higher de-differentiation scores were associated with higher tumor purity (p<0.001) and grade (p<0.001). Interestingly, by sorting tumors by their cancer stem cell phenotype we observed a strrong association with the recently described glioma molecular subtypes (p<0.001), which in turn is associated with the clinical outcomes (PFS, OS). The G-CIMP-low, Classical-like, Mesenchymal-like and LGm6-GBM samples, which have the worse outcomes, presented the highest cancer stem cell score. We defined molecular signatures of cancer stem cells that enabled classification of gliomas and identification of tumors with stem/progenitor-like phenotypes, associated with poor clinical outcome. Understanding undifferentiated phenotypes of glioma cells can improve our understanding of tumor biology and my pave the way for novel diagnostics and therapies for cancer patients.
Prominent Pulmonary Metastases Without Concurrent Osseous Involvement in Patients With High-Risk Neuroblastoma
Authors: Xia Bai, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2017)

Metastases from high-risk neuroblastomas generally are to the bone or bone marrow. Multiple lung metastases are rare, especially when there was no concurrent osseous metastasis. We report 2 cases of high-risk neuroblastomas having prominent lung metastases without concurrent osseous lesion observed.
Outcome reporting bias in clinical trials: why monitoring matters
Authors: John PA Ioannidis, Arthur L Caplan, Rafael Dal-Ré
Journal: BMJ (2017)

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MPTH-22. SERUM 2-HYDROXYGLUTARATE (2HG) LEVELS ARE CORRELATED WITH TISSUE 2HG LEVELS IN ISOCITRATE DEHYDROGENASE 1 AND 2 GENES (IDH1/2)-MUTATED GLIOMAS BUT NOT IN IDH1/2-WILDTYPE GLIOMAS
Authors: Makoto Ohno, Hiroaki Aikawa, Mitsuhiro Hayashi, Yuko Matsushita, Yasuji Miyakita, Masamichi Takahashi, Shunichiro Miki, Yosuke Kitagawa, Takahiro Yamauchi, Koichi Ichimura, Akinobu Hamada, Yoshitaka Narita
Journal: Neuro-Oncology (2016)

Mutations in isocitrate dehydrogenase 1 and 2 genes (IDH1/2) frequently occur in lower-grade gliomas and secondary glioblastomas. Mutant IDH1/2 proteins gain a new ability to produce the oncometabolite 2-hydroxyglutarate (2HG), however, the clinical impact of 2HG is not clear. In this study, we analyzed 2HG levels in both serum and tumor tissue and evaluated the role of 2HG in diffuse gliomas. We measured 2HG concentrations in 123 serums and in 78 tumor tissues by using liquid chromatography-tandem mass spectrometry method. IDH1/2 mutations status were determined by direct sequencing and/or immunohistochemistry. O-6-methylguanine DNA methyltransferase (MGMT) promoter methylations were analyzed using pyrosequencing and defined the mean level of methylation at the 16 CpG sites.Serum levels of 2HG in 42 patients with IDH-Mut tumors did not differ from those in 81 patients with IDH-WT tumors (median: 19.9 ng/mL for IDH-Mut vs 22.8 ng/mL for IDH-WT, p=0.86), however, tissue levels of 2HG in 28 patients with IDH-Mut tumors were significantly higher than those in 50 patients with IDH-WT tumors (median: 4.9 ug/mg for IDH-Mut vs 0.09 ug/mg for IDH-WT, p<0.0001). In 28 patients with IDH-Mut tumors, serum levels of 2HG were significantly correlated with tissue levels of 2HG (R2 = 0.39, p=0.0004), but in 50 patients with IDH-WT tumors, serum and tissue levels of 2HG did not show the relationship (R2 = 0.067, p=0.070). Tissue levels of 2HG showed a significant correlation with MGMT promoter methylations (R2= 0.15, p=0.0024).Our results suggest that tumor-derived 2HG is released in serum in the patients with IDH1/2 Mut tumors, however, their amounts are too small to detect the difference of serum 2HG levels in between patients with IDH-Mut and IDH-WT tumors. Accumulation of 2HG in tumor tissue may have an impact on MGMT promoter methylations.
Dynamics of neutrophil to lymphocyte ratio (NLR) predict effectiveness of PD1/PDL1 inhibition
Authors: M. Moschetta, B. Kasenda, G. Mak, M. Voskoboynik, N. Martynyuk, S. Rafii, V. Formica, H.-T. Arkenau
Journal: Annals of Oncology (2016)
Real-world effectiveness and safety of first-line bevacizumab (BEV) + paclitaxel (PAC) in &gt;2000 patients (pts) with HER2-negative metastatic breast cancer (mBC)
Authors: V. Mueller, M. Dank, S. de Ducla, L. Mitchell, A. Schneeweiss
Journal: Annals of Oncology (2016)
GENT-31. PEDcBIOPORTAL: A CANCER DATA VISUALIZATION TOOL FOR INTEGRATIVE PEDIATRIC CANCER ANALYSES
Authors: Pichai Raman, Adam C Resnick, Phillip B Storm, Sabine Mueller, Nikolaus Schultz, Ethan Cerami, John M Maris, Angela J Waanders
Journal: Neuro-Oncology (2016)

The pediatric cancer genome is severely under-represented in genomic databases as existing data portals have primarily focused on adult cancers. Furthermore, large-scale datasets like TARGET remain devoid of pediatric brain tumor data. To address this unmet need, we have developed a new cancer visualization tool (http://pedcbioportal.org). PedcBioPortal is an instance of cBioPortal supporting the curation and pan-cancer integration of published pediatric cancer data and consortia-based efforts including the Children’s Brain Tumor Tissue Consortium (CBTTC), the Pediatric NeuroOncology Consortium (PNOC), and the St. Baldrick’s Pediatric Stand Up 2 Cancer Dream Team. The aim of PedcBioPortal is to lower the barrier to large-scale pediatric and pan-cancer genomics analysis by providing rich visualizations and detailed statistics/summaries that integrate multi-dimensional datasets. Key functionalities include the ability to view mutations and copy number aberrations along the genome, correlations between gene expression profiles, and protein-protein interaction networks. Importantly, clinical trials data, pharmacological agent information, pathology reports, and tissue images are all incorporated, demonstrating the platform’s ability to store both structured and unstructured data. Researchers can also download data for further investigation and discovery efforts. Additionally, application program interfaces (APIs) that support bioinformatics and data scientist access to data for large-scale analyses projects are available. PedcBioPortal is part of an evolving cloud-based eco-system of applications dedicated to the empowered use of pediatric largescale data that encompass and integrate the translational cancer research workflow from a biospecimen availability, to processing of raw data, and interpretation of summarized data. As such, users can easily move between samples in PedcBioPortal to raw data files and even to physical specimens. PedcBioportal software is developed and maintained by a multi-institutional team, consisting of Memorial Sloan-Kettering Cancer Center, Dana Farber Cancer Institute, Princess Margaret Cancer Centre in Toronto, Children’s Hospital of Philadelphia, The Hyve in the Netherlands, and Bilkent University in Ankara, Turkey.