tbuckley/cabot-search huggingface dataset:
TMOD-10. MURINE AVATARS PERMIT STUDY OF GLIOBLASTOMA GENESIS AND PROGRESSION
Authors: Amin Kassam, Amber Lacrosse
Journal: Neuro-Oncology (2016)

Murine glioblastoma patient derived xenografts (PDX) hold great promise in the development of personalized, treatments. Additionally, murine avatars present an unparalleled opportunity to understand the mechanisms of GBM initiation, progression, migration and invasion, and resistance to treatment. The quality of the data obtained when using murine avatars is dependent upon the fidelity of the model system; that is, how closely does the PDX reproduce the clinical tumor with respect to molecular and biomarker features, tumor microenvironment, and microanatomical characteristics. We hypothesize that careful attention to location of tissue harvest, tissue handling, and adaptive culture techniques will result in faithful and reproducible avatars. Preoperative MRI diffusion-weighted imaging (DWI) permits localization of the component of the neoplasm with reduced apparent diffusion coefficient (ADC), a surrogate for increased cellularity. The surgical corridor is planned using 3D tractography to develop a trajectory to the this target within the subventricular zone (SVZ) for tissue harvest. Targeted tissue is harvested using a non-ablative suction and mechanical cutting device. Tissue is captured in a closed loop system to minimize atmospheric exposure and degradation. Tissue is maintained at 4 C, and constantly perfused by cold culture media. The tissue is transported to lab and processed into single cell suspension for subsequent sphere and laminin culture and ortho- and hetero-topic patient derived xenograft. Viable orthotopic GBM PDXs recapitulated histological and molecular features of the parent tumor. Specifically, migration away from the SVZ along white matter tracts was demonstrated. Preoperative identification of targets for tissue harvest and mindful maintenance of the tumor microenvironment throughout the collection and processing steps yields PDX that are highly reflective of the original tumor in regards to molecular and anatomical characteristics. This is critical when using murine avatars to develop treatments for and an understanding of the biology of GBM.
Incidence of Febrile Episodes During Stem Cells Mobilization After High Dose Cyclophosphamide Chemotherapy and G-CSF (filgrastim or lenograstim) Administration in Multiple Myeloma Patients: Preliminary Final Results.
Authors: Enrico Orciuolo, Gabriele Buda, Emerenziana Marturano, Elisa Mauro, Giuseppe Milone, Clotilde Cangialosi, Nicola Di Renzo, Domenico Pastore, Marino Brunori, Maria Pia Petrilli, Sergio Storti, Giuseppe Pietrantuono, Patrizio Mazza, Mario Petrini
Journal: Blood (2009)
Cancer Pain Assessment and Treatment Curriculum Guidelines. The Ad Hoc Committee on Cancer Pain of the American Society of Clinical Oncology.
Journal: Journal of Clinical Oncology (1992)

More than 70% of patients with cancer develop significant pain at some time during their illness. Despite the general consensus that most cancer pain can be treated effectively, many patients receive inadequate treatment of their pain. One significant contributing factor is the failure of health care professionals to receive formal training in this important aspect of oncology. The "Cancer Pain Assessment and Treatment Curriculum Guidelines" reflect the American Society of Clinical Oncology's commitment to providing optimal pain relief to patients with cancer. These guidelines represent an effort to promote formal instruction on the assessment and treatment of cancer pain in training programs and continuing education courses. The curriculum is broad in scope and applicable to patients of all ages. The guidelines emphasize the need for (1) routine pain assessment, (2) proficiency in prescribing opioids, nonopioid analgesics, and adjuvant medications, and (3) an understanding of the potential benefits of antineoplastic, anesthetic, neurosurgical, and behavioral approaches, which often require a coordinated multidisciplinary approach. The curriculum should prove a valuable guide to those who wish further education on the optimal treatment of cancer pain.
Phase 1/1b multicenter trial of the adenosine A2a receptor antagonist (A2aR) CPI-444 as single agent and in combination with atezolizumab (ATZ) in patients(Pts) with advanced cancers
Authors: A. Patnaik, J. Powderly, J. Luke, R. Miller, G. Laport
Journal: Annals of Oncology (2016)
Fatigue and Daily Life in Patients with Essential Thrombocythemia: Comparisons Between the USA and France in 447 Patients.
Authors: Ruben A. Mesa, Jerome Rey, Ayalew Tefferi, Joyce Niblack, Pascal Lenain, Emmanuel Raffoux, Thierry De Revel, John Camoriano, Jean-Jacques Kiladjian
Journal: Blood (2009)
Prognostic Significance of Magnetic Resonance Imaging (MRI) of Bone Marrow (BM) in Patients with Multiple Myeloma (MM) Undergoing Treatment with High-Dose Melphalan (HDM) and Autologous Stem Cell Transplantation (ASCT).
Authors: Athanasios Anagnostopoulos, Lia A. Moulopoulos, Maria Roussou, Efstathios Kastritis, Dimitra Gika, George Bozas, Aikaterini Stefanoudaki, Nikolaos Anagnostopoulos, Amalia Vassou, Konstantinos Bourantas, Meletios A. Dimopoulos
Journal: Blood (2006)
EXTH-44. NONE MGMT AND MMR DEPENDENT RADIOSENSITIZATION TO TREAT MALIGNANT GLIOMAS
Authors: Thierry Muanza, Slawomir Kumala, Jad Alshami, Mohamed Seyed Sadr, Thierry Muanza
Journal: Neuro-Oncology (2016)

GBM is the most common and devastating primary malignancy of the central nervous system in adults. The treatment of GBM remains difficult in that no contemporary treatments are curative with the current standard of care consisting of maximum safe resection surgery followed by radiotherapy with concomitant and adjuvant chemotherapy with Temozolomide (TMZ). GBM are characterized by high proliferative rate, aggressive invasiveness, high inter- and intra-tumor heterogeneity and limited response to radio- and chemotherapy. To date, O6-methylguanine DNA methyltransferase (MGMT) is the best characterized and the most clinically relevant modulator of chemoresistance in GBM. High level of MGMT activity in GBM cells (≥ 60% of patients) create a resistant phenotype by blunting the therapeutic effect of TMZ. Additionally, as recently proposed resistance to TMZ therapy also correlates with the Mismatch repair (MMR) activity in GBM tumors. Here, we demonstrate that the radiosensitizing abilities of ZRBA1, a binary DNA targeting alkylating agent and EGFR inhibitor does not depend on the GBM’s MGMT methylation status or their mismatch repair activity (MMR). Our studies have revealed that when combined with radiation, ZRBA1 significantly up-regulates multiple genes associated with signaling and repair of DNA damage. Moreover, proteome profiling studies have documented alternations in the phosphorylation pattern of several kinases involved in activation of cell stress related pathways including but not limited to: HSP27, c-Jun, ERK1/2 or STAT5a/b, CREB or MSK1/2. Overall our studies suggest that ZRBA1 in combination with radiation is a promising candidate for an effective combined modality treatment against GBM that can be used independently of newly diagnosed and recurrent patients ‘tumor MGMT or MMR status.
Analysis of Chimerism Induction Following Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with a Reduced-Intensity Regimen.
Authors: Rie Kojima, Yuji Heike, Jun Narumi, Shizuka Yamagata, Aki Chizuka, Kisato Nosaka, Masahiro Kami, Shin-ichiro Mori, Ryuji Tanosaki, Kensei Tobinai, Yoichi Takaue
Journal: Blood (2004)
Promoter shape varies across populations and affects promoter evolution and expression noise
Authors: Ignacio E Schor, Jacob F Degner, Dermot Harnett, Enrico Cannavò, Francesco P Casale, Heejung Shim, David A Garfield, Ewan Birney, Matthew Stephens, Oliver Stegle, Eileen E M Furlong
Journal: Nature Genetics (2017)
Phase I study of carboplatin, S-1 and concurrent thoracic radiotherapy for elderly patients with locally advanced NSCLC
Authors: Kageaki Watanabe, Seiji Niho, Kiyotaka Yoh, Koichi Goto, Yukio Hosomi, Hiroshi Tanaka, Hiroaki Okamoto, Keiji Nihei, Tetsuo Akimoto, Yuichiro Ohe
Journal: Annals of Oncology (2016)
Modified Drop Technique: Preparation of Smears for Automatic, Electronic Scanning2
Authors: William B. Courtney, Albert W. Hilberg, Samuel C. Ingraham, Raymond F. Kaiser, Mary M. Bouser
Journal: JNCI Journal of the National Cancer Institute (1960)

A modified application of the “drop technique” for cytology and its desirability for automatic, electronic scanning are discussed. Vaginal pool aspirates like all cytological specimens frequently have sparsely populated cellular material, and when the Cytoanalyzer is used, an optimum sampling of well-prepared specimens is desirable. Specimens are obtained by aspiration from the posterior vaginal fornix and suspended in 75 percent ethanol for fixation. This suspension is poured through a fine sieve and centrifuged; the supernatant is removed, the cellular material is diluted to a known density, and a known quantity of the specimen is dropped on a slide and spread over a previously defined area with the tip of the pipette. Feulgen staining is used to obtain a nuclear stain of medium intensity with minimal staining of the cytoplasm. A coverslip is mounted with Permount and the slide is ready for automatic scanning. Processing by this method provides an adequate control of the number, spacing, and distribution of cells in the smear without distorting their morphological characteristics.
OS7.5 Post-radiation cognitive impairment and hippocampal neuronal depletion measured by in-vivo metabolic MR spectroscopy: Final results of prospective investigational study
Authors: P. Pospisil, T. Kazda, P. Slampa, M. Bulik, M. Dobiaskova, J. Nahodilova, R. Jancalek
Journal: Neuro-Oncology (2016)
P05.01 Patient-derived xenograft (PDX) model of glioblastoma: from basic research to preclinical studies
Authors: A. Golebiewska, D. Stieber, A. Oudin, F. Azuaje, T. Kaoma, L. Vallar, A. Mock, C. Herold-Mende, R. Bjerkvig, S. P. Niclou
Journal: Neuro-Oncology (2016)

Animal models are essential tools for basic research and for preclinical therapeutic interventions. Although numerous clinical trials have been conducted, most fail due to inappropriate selection of the compounds at the preclinical stage. Therefore better preclinical models are crucial for achieving important clinical impact. Here we show that glioblastoma patient-derived xenografts (PDXs) based on organotypic spheroids represent a reliable and clinically-relevant animal model. Our PDX models are characterized by a tumor take rate close to 100% and a very reproducible tumor development time. We observe three distinct histological tumor phenotypes: a highly “invasive”, a highly “angiogenic” and an “intermediate” phenotype which combines invasion and vascular abnormalities. Typical glioblastoma characteristics such as pseudopalisading necrosis, invasion or microvascular proliferation are maintained. Interestingly, angiogenic features appear stronger in nude rats compared to immunodeficient mice. We show that PDXs retain the genetic and epigenetic profiles of transplanted tumor cells of patient biopsies through several generations. Genome-wide transcriptomic profiles of PDXs are similar to patient biopsies and correlate better with TCGA glioblastoma samples than conventional glioma cell lines. Differences at the transcriptomic level can be largely explained by the replacement of human stromal cells in the mouse brain, which impact molecular subclassification of PDXs. Interestingly, although stem-cell associated heterogeneous profiles are retained upon xenografting, they appear dependent on the tumor microenvironment. The model can be applied for analyses at different molecular levels including genomic, transcriptomic, proteomic and metabolomic data. Using eGFP-expressing NOD/Scid mice allows to discriminate tumor and stromal cell populations and to characterize in depth intra-tumoral heterogeneity. Importantly, the PDXs can be applied for accurate reproducible pre-clinical trials, including personalized medicine-based treatments. The use of this model should lead to a better evaluation of the efficacy of novel drugs, and increase the success of follow-up clinical studies. Although the use of immunodeficient animals limits potential applications for immune therapies, the role of microglia and macrophages - the main immune component of glioblastomas - can still be addressed in nude mice.
NTOX-03. HIGH RATE OF METHOTREXATE-INDUCED LEUKOENCEPHALOPATHY IN ADULT PATIENTS WITH CNS LYMPHOMA CARRYING MTHFR SINGLE GENE POLYMORPHISMS
Authors: Sylvia Eisele, Corey Gill, SooAe Jones, Michelle Pisapia, Tracy Batchelor, Scott Plotkin, Jorg Dietrich
Journal: Neuro-Oncology (2016)

High-dose methotrexate (HD-MTX) is a key component of chemotherapy for CNS lymphoma (CNSL) but can be associated with leukoencephalopathy. The methylenetetrahydrofolate reductase (MTHFR) gene single-nucleotide polymorphisms (SNPs) C667T and A1298C reduce MTX metabolism and may increase the risk for systemic toxicity following HD-MTX. The correlation of these SNPs with neurotoxicity has not been evaluated. We performed a retrospective study on 52 patients (female n=20, male n=32) with CNSL who tested positive for MTHFR C677T and/or A1298 and who received HD-MTX (> 3.5 gm/m2) as part of their induction chemotherapy. MRI T2/FLAIR changes were assessed (grade 0=no abnormalities, grade 1=mild white matter changes, grade 2= pronounced and diffuse bilateral T2 hyperintensities) at baseline, 6, 12, and 60 months following treatment.Of all 52 patients, 30 harbored MTHFR C677T (n=10 homozygote, n=20 heterozygote), 14 had MTHFR A1298C (n=11 heterozygote, n=3 homozygote), and eight patients were compound heterozygote. We observed a high rate of progressive white matter changes compared to the literature which estimates a 25% incidence of leukoencephalopathy in this patient population. At 12 months, 33/52 patients (64%) showed T2/FLAIR abnormalities within the cerebral white matter (grade 1, n=27 (52%); grade 2, n=6 (12%)). At 60 months, presence of white matter changes increased to 38/52 (73%; grade 1, n=27 (52%); grade 2, n=11 (21%)). There was no significant difference in frequency of neurotoxicity between MTHFR subtypes. We observed two distinct radiographic patterns of white matter changes: a patchy, multifocal white matter T2/FLAIR hyperintensity and a more diffuse homogenous bi-hemispheric leukoencephalopathy. Our study is limited by its small sample size and retrospective design. A larger prospective radiographic and neurocognitive analysis with comparison to patients with MTHFR wildtype status would allow for a better characterization of the estimated risk, radiographic progression pattern, and functional consequences of chemotherapy associated white matter changes in CNSL patients.
A Prospective Randomised Trial of Targeted Therapy for Diffuse Large B-Cell Lymphoma (DLBCL) Based upon Real-Time Gene Expression Profiling: The Remodl-B Study of the UK NCRI and SAKK Lymphoma Groups (ISRCTN51837425)
Authors: Andrew J Davies, Josh Caddy, Tom Maishman, Sharon Barrans, Christoph Mamot, Matthew Care, Christopher Pocock, Louise Stanton, Debbie Hamid, Keith Pugh, Andrew McMillan, Paul Fields, Anton Kruger, Andrew Jack, Peter W. M. Johnson
Journal: Blood (2015)
Characteristics of Sarcoidosis-Associated Immune Thrombocytopenia: a Consecutive Study of 20 Cases.
Authors: Matthieu Mahévas, Laurent Chiche, Medhi Khellaf, Yurdagu Uzunhan, Anne-Sophie Morin, Véronique Perronne, Louis Affo, Olivier Lidove, Jean-Pierre Ducroix, Thomas Papo, Yves Pacheco, Nicolas Schleinitz, Marc Michel, Dominique Valeyre, Bertrand Godeau
Journal: Blood (2009)
Phase I Trial of Oral Vorinostat (Suberoylanilide Hydroxamic Acid, SAHA) in Combination with Bortezomib in Patients with Advanced Multiple Myeloma.
Authors: Donna M. Weber, Sundar Jagannath, Amitabha Mazumder, Ronald Sobecks, Gary J. Schiller, Maria Gavino, Chantelle Sumbler, Carrie McFadden, Cong Chen, Justin L. Ricker, Syed Rizvi, Carol Oerth, Patricia Brownell, Mohamad A. Hussein
Journal: Blood (2007)
Combination of MEDI0680, an anti-PD-1 antibody, with durvalumab, an anti-PD-L1 antibody: A phase 1, open-label study in advanced malignancies
Authors: O. Hamid, L.Q. Chow, R.E. Sanborn, S. Marshall, C. Black, M. Gribbin, J. McDevitt, J.J. Karakunnel, J.E. Gray
Journal: Annals of Oncology (2016)
Survival of Patients with Clinically Identified Monoclonal B-Cell Lymphocytosis (MBL) Relative to the Age and Sex Matched General Population
Authors: Tait Shanafelt, Neil E. Kay, Kari Rabe, Timothy Call, Clive S. Zent, Susan Schwager, Jose Leis, Diane F. Jelinek, Susan Slager, Curtis Hanson
Journal: Blood (2010)
Positron emission tomography (PET) with <sup>89</sup>Zr-labeled trastuzumab (<sup>89</sup>Zr-trastuzumab): Monitoring HER2 expression in HER2-positive gastric cancer in vivo.
Authors: Y. Y. Janjigian, N. T. Villegas, J. P. Holland, M. A. Shah, V. Divilov, D. P. Kelsen, J. S. Lewis
Journal: Journal of Clinical Oncology (2011)

35 Background: The ToGA study established HER2 is a target in the treatment of gastric cancer. Trastuzumab pharmacokinetics and organ distribution is varied in each patient and is heavily affected by the extent of tumor load (Oude Munnink, JCO 2010). 89 Zr-trastuzumab HER2 PET can be used to image that variability and may aid in detection and staging of HER2-positive tumors. We are implementing 89 Zr-radiolabeled trastuzumab PET in vivo for imaging of HER2-positive gastric cancer and for future non-invasive assessment of HER2 inhibition with a dual irreversible HER1/HER2 inhibitor, BIBW-2992. Methods: 89 Zr (t 1/2 = 3.17 days) was prepared via the 89 Y(p,n) 89 Zr transmutation with high radiochemical yields (1.52±0.11 mCi/μAh) and purity (&gt;99.99%). Trastuzumab was functionalized with the tris-hydroxamate chelate, desferrioxamine B (DFO) and radiolabeled with [ 89 Zr]Zr-oxalate at room temperature. 89 Zr-trastuzumab PET experiments in athymic nu/nu mice bearing sub-cutaneous NCI-N87 (HER2+) and/or SNU1 (HER2-) tumors were conducted. NCI-N87 gastric cancer cells were treated with BIBW-2992. Results: 89 Zr-trastuzumab radiolabeling proceeded in high radiochemical yield and specific-activity of 2.82±0.05 mCi/mg. In vitro assays demonstrated &gt;99% radiochemical purity with an immunoreactive fraction of 0.87±7. In vivo biodistribution experiments revealed high and specific uptake in HER2-positive tumors after 72 h (85.2±11.1% ID/g) with retention of activity for over 120 h. No uptake was seen in HER2-negative gastric cancer xenografts. In vitro, BIBW-2992 demonstrates dose dependent growth inhibition in the HER2+ gastric cancer cell line. Conclusions: 89 Zr-trastuzumab provides quantitative and highly-specific delineation of HER2-positive gastric cancer. In vivo studies of BIBW2-2992 in gastric cancer with 89 Zr-trastuzumab HER2 PET response assessment are underway. A Phase I study of 89 Zr-trastuzumab PETin HER2-positive patients is to open at MSKCC imminently. No significant financial relationships to disclose.
Kan-Wen Ma
Authors: J A Jewell, Sheila Hillier
Journal: BMJ (2017)

Kan-Wen Ma was a distinguished authority on the history of Chinese medicine. In China, he is credited with establishing the term “traditional Chinese medicine” (TCM) for the treasure house of knowledge that exists in ancient texts. He introduced Western audiences to a wider understanding of the antiquity of TCM and the complex and subtle contributions of its practitioners. His special academic interest was comparisons between traditional Chinese medical thinking and European and Islamic medical thought from the earliest times. In his lifetime, he published or edited 12 books and 160 academic papers despite suffering and having his career blighted by the chaos of the Cultural Revolution in China in the 1960s and 1970s.

Few academics could have experienced the vicissitudes of life in 20th century China and created not one, but two successful careers, first in Mao’s China and later in the more peaceful environment of the University of London. Towards the end of his life, at UCL, he was working to complete a wide ranging study of the interaction between the Western medical missionary movement in China and traditional Chinese medicine in the 19th and early 20th centuries.

Kan-Wen Ma was born in Beijing in 1927 into a family who numbered traditional physicians among its members. His father was head of a secondary school in Beijing. He was at school when the Japanese invaded China in the 1930s. This made home life challenging and studies difficult, but in 1945 he gained entrance to the elite Yenching University, where he studied history and philosophy of science. Yenching, founded by Christian missionaries and funded through American philanthropy, offered a Western style university education. He became fluent in English and appreciative of British and American culture, …
Efficacy and Safety of Posaconazole (POS) in the Treatment of Refractory Invasive Fungal Infections (rIFIs) in Patients with Underlying Renal Impairment.
Authors: Amelia A. Langston, Donald R. Graham, J. Richard Graybill, Lisa D. Pedicone, Issam I. Raad
Journal: Blood (2005)
The Hematopoietic Supportive Function of Adult Bone Marrow Mesenchymal Stem Cells Is Lost after Differentiation Induction towards Adipocytic, Osteoblastic and Vascular Smooth Muscle Lineages
Authors: Tatiana Ribeiro, Aurelie Picard, Elfi Ducrocq, Alain Langonne, Philippe Rosset, Olivier Herault, Jorge Domenech
Journal: Blood (2008)
Distinct Expression Patterns of microRNAs in Activated B Cell (ABC) and Germinal Center B (GC) Subtypes of Diffuse Large B Cell Lymphoma (DLBLC).
Authors: Jean-Noel Bastie, Jean-Philippe Jais, Thierry Molina, Emmanuelle Come, Bertrand Coiffier, Christian Gisselbrecht, David Rickman, Aurelien de Reynies, Josette Briere, Philippe Gaulard, Pierre Feugier, Herve Tilly, Gilles Salles, Corinne Haioun, Karen Leroy
Journal: Blood (2007)
Results of a Phase I Dose Escalation Study of the Novel, Oral CRM1 Selective Inhibitor of Nuclear Export (SINE) KPT-335 in Dogs with Spontaneous Non-Hodgkin's Lymphomas (NHL)
Authors: Sharon Shacham, Sandra Barnard, William Kisseberth, Daisuke Ito, Kiersten Jensen, Antonella Borgotti, Michael Henson, Heather Wilson, Dilara McCauley, Jaime Modiano, Michael Kauffman, Cheryl London
Journal: Blood (2012)
Considering Blood Pressure Level in the Association Between Serum Calcium Level and the Size and Expansion in Patients With Intracerebral Hemorrhage
Authors: Wei Chen, Li Wang, Jing Chen
Journal: JAMA Neurology (2017)

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