tbuckley/cabot-search huggingface dataset:
Inactivation of Pre-B Cell Receptor-Mediated Tumor Suppression by Aberrant Splicing in Ph+ Acute Lymphoblastic Leukemia.
Authors: Cihangir Duy, Mieke Sprangers, Lars Klemm, Rahul R. Nahar, Daniel Nowak, Giovanni Martinelli, Wolf-Karsten Hofmann, Phillip H Koeffler, Hassan Jumaa, Markus Müschen
Journal: Blood (2009)
RBIO-04. FRACTAL STRUCTURE IN THE VOLUMETRIC CONTRAST ENHANCEMENT OF MALIGNANT GLIOMAS AS A MARKER OF OXIDATIVE METABOLIC PATHWAY GENE EXPRESSION
Authors: Kai Miller, Sharon Berendsen, Tatjana Seute, Kristen Yeom, Melanie Gephardt, Gerald Grant, Pierre Robe
Journal: Neuro-Oncology (2016)

Fractal structure is found throughout many processes in nature, and often arises from sets of simple rules. We examined the contrast enhancement patterns in MRI scans from glioblastoma patients for evidence of fractal structure and correlated these with gene expression patterns. For 39 glioblastoma patients, volumetric T1 post-contrast MRI scans were obtained before surgical resection. For each tumor, we calculated the fractal dimension (Minkowski–Bouligand dimension) of contrast enhancement with a box-counting (cubic scaling) approach. RNA expression microarray data from resected tissue were explored by gene set enrichment analysis (GSEA), and VEGF expression level was determined by antibody staining of resected tissue. We found robust evidence for fractal structure in the contrast enhancement pattern, with an average fractal dimension of 2.17 ± 0.10, with a visually apparent split at 2.10. GSEA analysis showed a clear association between this split in fractal dimension and 6 gene sets (of 4080), all 6 of which are linked to mitochondrial respiration/ATP production pathways. Higher fractal dimension (>2.10) was associated with decreased gene expression in all cases. VEGF expression was correlated with higher fractal dimension. There is fractal structure in the volumetric enhancement pattern of glioblastomas, with dimension approximately 2.15. Variation in this fractal dimension, and therefore the complexity of contrast enhancement it reflects, is specifically associated with genetic correlates of a shift to glycolytic metabolism in tumor cells. Drugs that shift glioblastoma to oxidative metabolism have recently been identified as independent therapeutic agents as well as sensitizing agents for irradiation. Therefore, a radiogenomic marker of glucose metabolism, such as this fractal structure in enhancement, might help to guide individualized therapy.
Th1 epitopes as potential biomarkers for ipilimumab treatment
Authors: J.P. Marquez, E. Ramos, D.R. Herendeen, K. Quayle, M.L. Verburg, A. Suplee-Rivera, S. Carrillo, J.A. Matute-Briseno, R. Soto-Soto, A. Camacho-Hernandez, P.A. Lucero-Diaz
Journal: Annals of Oncology (2016)
Approaches for quantifying antimicrobial consumption per animal species based on national sales data: a Swiss example, 2006 to 2013
Authors: Luís P Carmo, Gertraud Schüpbach-Regula, Cedric Müntener, Anne Chevance, Gérard Moulin, Ioannis Magouras
Journal: Eurosurveillance (2017)

Antimicrobial use in animals is known to contribute to the global burden of antimicrobial resistance. Therefore, it is critical to monitor antimicrobial sales for livestock and pets. Despite the availability of veterinary antimicrobial sales data in most European countries, surveillance currently lacks consumption monitoring at the animal species level. In this study, alternative methods were investigated for stratifying antimicrobial sales per species using Swiss data (2006-2013). Three approaches were considered: (i) Equal Distribution (ED) allocated antimicrobial sales evenly across all species each product was licensed for; (ii) Biomass Distribution (BMD) stratified antimicrobial consumption, weighting the representativeness of each species' total biomass; and (iii) Longitudinal Study Extrapolation (LSE) assigned antimicrobial sales per species based on a field study describing prescription patterns in Switzerland. LSE is expected to provide the best estimates because it relies on field data. Given the Swiss example, BMD appears to be a reliable method when prescription data are not available, whereas ED seems to underestimate consumption in species with larger populations and higher treatment intensity. These methods represent a valuable tool for improving the monitoring systems of veterinary antimicrobial consumption across Europe.
NIMG-71. TIME-TO-OCCURRENCE OF GLIOBLASTOMA ON MRI
Authors: Tessa Churchill, Pratish Shah, Benjamin Liu
Journal: Neuro-Oncology (2016)

Gadolinium-based contrast enhanced MRI is the standard neuroimaging for evaluation of glioblastoma multiforme (GBM). After onset of neurologic symptoms, identification of a heterogeneously enhancing mass is the typical imaging feature of GBM. However, the time-to-occurrence of GBM on MRI is not well studied. A single-center, retrospective cohort of patients having brain tumor resection and a pathological diagnosis of GBM between 2011 and 2015 was performed. The neuroimaging of 281 GBM patients were reviewed, and those patients with prior negative brain MRI were included. 14 patients were identified, ages 37-78 y/o, median 66.5 y/o, average 63 y/o, 10 men, 4 women. Median time between patient’s prior negative brain MRI and subsequent MRI demonstrating GBM was 2.2 years (range 10 months – 8.5 years; average 3.2 years). All patients developed a heterogeneously enhancing mass with surrounding FLAIR hyperintensity on the presenting MRI. Review of the prior MRI demonstrated no abnormal enhancement nor any nonenhancing FLAIR abnormality in the location of the subsequent tumor. Molecular testing was performed on 13 cases, and revealed all were IDH1 wildtype. IDH1 status is unknown for one case. Tumor location, average size, and indications for prior MRI were also characterized. A study of the time-to-occurrence of GBM on MRI demonstrated a median of 2.2 years between a prior negative brain MRI and development of GBM on a subsequent brain MRI. The shortest time to development of a GBM from a negative brain MRI was 10 months. These findings are important for the understanding of the natural history of GBM.
Complement Genotype and Multiparametric Laboratory Analysis to Predict Response to Eculizumab and to Adjust Treatment in Patients with Paroxysmal Nocturnal Hemoglobinuria
Authors: Marta Subías-Hidalgo, Alicia Lopez, Jaouad Anter, Sheila Pinto, Emilio Ojeda, Jose A Garcia-Marco, Fernando Ataulfo Gonzalez-Fernandez, Rafael Fores, Laura Llorente, Ana Maria Villegas-Martinez, Santiago Rodriguez-Cordoba
Journal: Blood (2015)
Trastuzumab (H) treatment in patients (pts) with metastatic breast cancer (MBC): An observational retrospective study in four hospitals from Bogotá, Colombia (ONCOLGroup study)
Authors: H. Carranza, A. F. Cardona, C. Vargas, J. M. Otero, J. O. Sánchez, E. Carrasco-Chaumel, L. Reveiz, D. Torres, C. Castro, A. M. González-Angulo
Journal: Journal of Clinical Oncology (2009)

e12016 Background: Breast cancer is the second most common cancer diagnosed in Colombian women, and approximately 26% of MBC are HER-2-positive in our population. The purpose of this study was to assess the characteristics and outcome of pts with HER-2-positive MBC treated with H-based therapy in Bogotá. Methods: This retrospective study included 119 pts treated between 2000 and 2007. Overall response rates (ORR), clinical benefit (CB), time to progression (TTP), and overall survival (OS) were estimated. Most common grade 2/3 toxicities are reported as well as variables that influenced survival. Results: Median age was 62 years (range, 37 to 75). Eighty-seven (73%) pts had recurrent disease and the rest had de novo MBC. Performance status was ≥70% in 114 pts, 66% had ≤2 metastatic sites, and 58% had hormone receptor positive disease. Previous adjuvant therapy before H included antracyclines in 68% and taxanes in 39% of the pts. H was part of the first-line therapy for MBC in 86.5% of the pts, leading to a 54% ORR in 103 evaluable pts. CB was 81% and median TTP was 6.1 months. (range, 1.2 to 26 mo). The most common toxicities in this setting included neutropenia ≥G3 (9%) and neuropathy ≥G3 (7%). H was given as part of second line therapy to 54 (45%) pts, but only 41 had evaluable disease. A 56% ORR was found in this subgroup, 85% CB and 4.7-month median of TTP. Grade ≥G3 hand-foot syndrome was the main toxicity (14%). Median OS after the diagnosis of MBC was 23 months (range, 1.6–93 mo), being longer for pts with HR-positive disease (p = 0.036), in pts with loco-regional relapse (p = 0.029), and in those older than 50 (p = 0.0025). Only two variables independently predicted OS: age (HR: 0.4, 95% CI: 0.35–0.93, p = 0.046) and HR status (HR: 0.7, 95% CI: 0.60–0.86, p = 0.040). Two pts (1.7%) had H-induced heart failure. Conclusions: H in combination with chemotherapeutic agents has been proved to be an effective and safe treatment for HER-2-positive MBC. The results from our series agreed with those reported in the medical literature and guarantee the regular use of H in Colombia. No significant financial relationships to disclose.
Gemtuzumab Ozogamicin (GO) and Continuous Infusion Cytarabine (ARA-C) for Relapsed/Refractory Acute Myeloid Leukemia (AML) Prior to Allogeneic Stem Cell Transplantation (SCT).
Authors: Amer Zeidan, Wei Tan, Gregory Wilding, LaurieAnn Ford, Theresa Hahn, Shannon Smiley, Minoo Battiwalla, Philip L. McCarthy, Eunice S. Wang, Meir Wetzler
Journal: Blood (2008)
RECOURSE trial: Performance status at discontinuation in patients receiving trifluridine/tipiracil (TAS-102)
Authors: E. Van Cutsem, R. Garcia-Carbonero, A. Pastorino, A. Zaniboni, A. Falcone, N. Amellal, F. Benedetti, R. Mayer, A. Ohtsu, J. Tabernero
Journal: Annals of Oncology (2016)
DDIS-03. A NOVEL BBB-PERMEABLE CHEMOTHERAPEUTIC AGENT FOR THE TREATMENT OF GLIOBLASTOMA
Authors: Theo Nicolaides, Tomoko Ozawa, Michael Prados, Tsun Wen Yao, Wolf-Nicolas Fischer, Bernd Jandeleit, Kerry Koller
Journal: Neuro-Oncology (2016)

Standard of care for Glioblastoma (GBM) patients is surgical tumor resection, followed by radiation and chemotherapy with temozolomide (TMZ). Unfortunately, 60% of newly diagnosed GBM patients express high levels of the DNA repair enzyme MGMT and are TMZ-insensitive, and all patients eventually become refractory to treatment. The blood-brain barrier (BBB) remains an obstacle to adequate delivery of chemotherapeutic agents to brain tumors. Lipophilic drugs such as TMZ and lomustine (CCNU) are able to cross the BBB via passive diffusion; however, their non-selective transport also causes toxicity to critical systemic organs, such as the bone marrow, leading to dose-limiting toxicity. BBB-permeable chemotherapeutic agents that are efficacious in TMZ-insensitive and refractory patients are needed. The large amino acid transporter 1 (LAT1) is highly expressed on the BBB and in GBM, where it is associated with poor prognosis, but is undetectable in normal brain tissue. Targeting LAT1 transport, while avoiding interaction with other closely related transporters expressed on normal tissue such as LAT2, will target brain tumors and avoid uptake into healthy tissue. We report the generation of a novel molecule (QBS10072S) that combines a potent cytotoxic domain with the structural features of a selective LAT1 substrate. QBS10072S is 50-fold more selective for LAT1 vs. LAT2, and demonstrates significant in vitro cytotoxicity to LAT1-expressing GBM cell lines and minimal cytotoxicity to normal human astrocytes (LAT1-negative). Unlike TMZ, QBS10072S is cytotoxic to cells with both high and low MGMT expression. In orthotopic GBM xenografts, QBS10072S causes significant delay in tumor growth and increase in mouse survival vs. vehicle or TMZ. QBS10072S is well tolerated, with no myelosuppression in mice dosed up to three times a week and no toxicity to BBB or normal brain cells. In summary, QBS10072S is a novel BBB-permeable chemotherapeutic agent with the potential to treat TMZ-insensitive and recurrent GBM.
Telemedicine in Pediatric Cardiology: A Scientific Statement From the American Heart Association
Authors: Gary M. Satou, Karen Rheuban, Dale Alverson, Mark Lewin, Christopher Mahnke, James Marcin, Gerard R. Martin, Lisa Schmitz Mazur, David J. Sahn, Sanket Shah, Reed Tuckson, Catherine L. Webb, Craig A. Sable
Journal: Circulation (2017)
Epacadostat plus pembrolizumab in patients with advanced melanoma and select solid tumors: Updated phase 1 results from ECHO-202/KEYNOTE-037
Authors: T.C. Gangadhar, O. Hamid, D.C. Smith, T.M. Bauer, J.S. Wasser, A.J. Olszanski, J.J. Luke, A.S. Balmanoukian, D.R. Kaufman, Y. Zhao, J. Maleski, M.J. Jones, L. Leopold, T.F. Gajewski
Journal: Annals of Oncology (2016)
Circulating cell-free DNA can predict relapse after resection of metastatic liver tumors from colorectal cancer
Authors: T. Iwai, T. Yamada, G. Takahashi, S. Matsumoto, M. Koizumi, S. Shinji, A. Matsuda, Y. Yokoyama, K. Hara, K. Takeda, M. Nakayama, S. Kitano, K. Ohta, E. Uchida
Journal: Annals of Oncology (2016)
MicroRNA Expression Profiling Characterize Diffuse Large B-Cell Lymphomas and Follicular Lymphomas.
Authors: Anja Roehle, Kai P. Hoefig, Dirk Repsilber, Christoph Thorns, Kai O. Wesche, Christian Kaehler, Wolfram Klapper, Michael Pfreundschuh, Marita Ziepert, Markus Loeffler, Hartmut Merz, Alfred C. Feller
Journal: Blood (2007)
Quantitative Analysis of AID Expression and Somatic Hypermutation Identifies Isotype-Switched and Non-Switched Follicular Lymphomas As Distinct Biological Subgroups,
Authors: Florian Scherer, Cristina Bertinetti-Lapatki, Marcus Duehren-von Minden, Joachim Boehm, Hendrik J. Veelken
Journal: Blood (2011)
IMST-46. DENDRITIC CELL-BASED IMMUNOTHERAPY FOR MALIGNANT GLIOMA BY WAY OF A NOVEL DENDRITIC CELL-TARGETED (scFvDEC205) ADENOVIRAL VECTOR
Authors: Julius W Kim, J.Robert Kane, Jacob Young, Dou Yu, Jason Miska, Alan Chang, Aida Rashidi, Atique Ahmed, Irina Balyasnikova, Maciej Lesniak
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is a deadly brain malignancy with a mean patient survival of just over one year with standard modes of treatment. As such, new and more efficacious modes of treatment are direly necessitated. In this context, dendritic cells (DCs), the most potent antigen presenting cells, have emerged as essential targets for anti-tumor vaccination over the past four decades and are a promising avenue where innovation has great translational potential. However, complicated realities have thwarted the enthusiasm of DC vaccines given the lack of specific in vivo DC-targeted delivery vehicles and an inability to induce robust effector CD8+T cell responses that has led to an underwhelming anti-tumor T cell response. Based on this understanding, we engineered a DC-selective vector, Ad5scFv205FF by incorporating a single chain antibody against DEC205 which is selectively expressed in DCs. After confirming the genetic engineering of the fiber modification, we analyzed the tropism of this novel DC-targeted delivery vehicle. The vector, as we expected, lost its natural tropism (coxsackie and adenovirus receptor expressing cells) and gained a new, DC-selective tropism both in vitro and in vivo. We also investigated the therapeutic efficacy of Ad5scFvDEC205FF in a murine model of GBM and observed highly efficient vaccination oriented survival benefit. Further, we will discuss a capability of Ad5scFvDEC205FF infected DCs as a therapeutic reagent(s) carrier to modulate the immunosuppressive microenvironment of glioma. This work collectively represents a novel anti-glioma vaccination, enhanced by the in vivo selective delivery of the tumor antigen that will provide a platform for the evaluation and translation of highly promising glioma immunotherapy strategies.
Acetaminophen in Pregnancy and Adverse Childhood Neurodevelopment
Authors: Norman R. Saunders, Mark D. Habgood
Journal: JAMA Pediatrics (2017)

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GENT-41. CHARACTERIZING AND THERAPEUTICALLY TARGETING G-QUADRUPLEX DNA IN ATRX-MUTANT GLIOMA
Authors: Yuxiang Wang, Carla Danussi, Peter Lansdorp, Adriana Heguy, Jason Huse
Journal: Neuro-Oncology (2016)

Recent genomic studies have identified recurrent ATRX mutations in lower grade gliomas (LGGs), especially WHO grade II and III astrocytomas. As a chromatin remodelling protein, ATRX is thought to guard against genomic instability in part by regulating the formation of deleterious secondary structures in DNA known as G-quadruplexs (G4s). In the cell, G4s represent a source of stress for DNA replication by inducing stalled replication forks. In this study, we found by immunostaining in isogenic astrocyte models that ATRX deficiency increased nuclear G4 formation. Moreover, genomic pull-down with a G4-specific antibody showed enrichment in ATRX-deficient astrocytes, which was associated with increased nuclear gamma-H2AX and upregulated ATR pathway signaling. No immediate effects on proliferation, cell cycle progression, or apoptosis were observed, the latter most likely due to coincident TP53 loss in our cell line models. We are currently investigating the precise genomic consequences of increased G4s in the ATRX-deficient setting, particularly with regard to oncogenic copy number alterations that may accumulate over time. We also demonstrated that increased G4s may be therapeutically targetable by G4-stabilizing reagents. One of these compounds, Quarfloxin (CX3543), selectively inhibits cell growth in ATRX-deficient astrocytes at concentrations between 25-300nM. In so doing, Quarfloxin also upregulates DNA damage responses (gamma-H2AX) and apoptotic (Annexin-V) markers in ATRX-deficient astrocytes to a significantly greater extent than in wild type counterparts. Notably, the degree of cell cycle arrest induced by Quarfloxin, did not vary with ATRX status. Accordingly, preferential growth inhibition, induced by Quarfloxin in the ATRX-deficient setting, is likely due to increased apoptosis rather than cell cycle arrest. We are continuing to evaluate the therapeutic potential of Quarfloxin in disease-relevant model systems. Such synthetic lethality represents a promising strategy to effectively target ATRX-deficient tumors.
Cancer Stem Cells Regulate Cancer-Associated Fibroblasts via Activation of Hedgehog Signaling in Mammary Gland Tumors
Authors: Giovanni Valenti, Hazel M. Quinn, Guus J.J.E. Heynen, Linxiang Lan, Jane D. Holland, Regina Vogel, Annika Wulf-Goldenberg, Walter Birchmeier
Journal: Cancer Research (2017)

Many tumors display intracellular heterogeneity with subsets of cancer stem cells (CSC) that sustain tumor growth, recurrence, and therapy resistance. Cancer-associated fibroblasts (CAF) have been shown to support and regulate CSC function. Here, we investigate the interactions between CSCs and CAFs in mammary gland tumors driven by combined activation of Wnt/β-catenin and Hgf/Met signaling in mouse mammary epithelial cells. In this setting, CSCs secrete the Hedgehog ligand SHH, which regulate CAFs via paracrine activation of Hedgehog signaling. CAFs subsequently secrete factors that promote expansion and self-renewal of CSCs. In vivo treatment of tumors with the Hedgehog inhibitor vismodegib reduce CAF and CSC expansion, resulting in an overall delay of tumor formation. Our results identify a novel intracellular signaling module that synergistically regulates CAFs and CSCs. Targeting CAFs with Hedgehog inhibitors may offer a novel therapeutic strategy against breast cancer. Cancer Res; 77(8); 2134-47. ©2017 AACR.
The Enduring Legacy of 250 Years of Pharmacology in Edinburgh
Authors: John S. Kelly, Angus V.P. Mackay
Journal: The Annual Review of Pharmacology and Toxicology (2017)

In 1768, 250 years ago, the University of Edinburgh appointed Francis Home to the first chair of materia medica, the accumulated knowledge of materials used in healing. Francis Home and his colleagues were determined to improve the quality of medical training in Edinburgh by introducing a final examination and compiling a catalog of medicines validated by the Royal College of Physicians of Edinburgh. The catalog, known as the Edinburgh Pharmacopoeia, was a great success, partly due to the orderly nature of its contents, its routine editing to eliminate worthless entries, and the introduction of new treatments whose preparation was precisely documented. In a relatively short time, the worth of the Edinburgh Pharmacopoeia was recognized throughout Europe, America, and the British Empire. Today, the British and European Pharmacopoeias are catalogs of publicly available, legally enforceable standards for active pharmaceutical ingredients and finished dosage forms of pharmaceutical products and medical devices. Home and the many luminaries who succeeded him would surely take pleasure and pride in the fact that the mantra of today's medicines regulators worldwide is little different from that of these early visionaries: "To take better advantage of the best possible science in the service of the public health and our health-care systems" ( 1 , p. 492).
Addition of Bortezomib (Velcade™) to High Dose Melphalan (Vel-Mel) as an Effective Conditioning Regimen with Autologous Stem Cell Support in Multiple Myeloma (MM).
Authors: Klaus Hollmig, Julie Stover, Giampalamo Talamo, Maurizio Zangari, Raymond Thertulien, Frits van Rhee, Athanasios Fassas, Elias Anaissie, Guido Tricot, Bart Barlogie
Journal: Blood (2004)