tbuckley/cabot-search huggingface dataset:
Tipifarnib (ZARNESTRATM in Previously Untreated Poor-Risk AML of the Elderly: Updated Results of a Multicenter Phase 2 Trial.
Authors: Jeffrey E. Lancet, Jason Gotlib, Ivana Gojo, Eric J. Feldman, Lawrence Morris, Alain Thibault, Jane L. Liesveld, Jacqueline Greer, Kathleen Dugan, Mitch Raponi, John J. Wright, Peter L. Greenberg, Judith E. Karp
Journal: Blood (2004)
A novel approach for the identification of efficient combination therapies in primary human acute myeloid leukemia specimens
Authors: I Baccelli, J Krosl, G Boucher, I Boivin, V-P Lavallée, J Hébert, S Lemieux, A Marinier, G Sauvageau
Journal: Blood Cancer Journal (2017)

Abstract Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations. Initially conducted with a selected library of 5000 small molecules and 20 primary AML specimens, it reveals 5 broad classes of sensitized therapeutic target pathways along with their synergistic patient-specific fingerprints. This novel method opens new avenues for the development of AML personalized therapeutics and may be generalized to other tumor types, for which in vitro cancer stem cell cultures have been developed.
REINVENT (REgorafenIb traNslational eValuation angiogENesis proTocol)
Authors: L. Demurtas, E. Lai, A. Cubeddu, M. Puzzoni, G. Pusole, S. Tolu, A. Dessì, R. Mascia, V. Pusceddu, G. Astara, C. Madeddu, E. Massa, P. Ziranu, L. Orgiano, L. Casula, M. Scartozzi
Journal: Annals of Oncology (2016)
Adenosine A2A receptor antagonist, CPI-444, blocks adenosine-mediated T cell suppression and exhibits anti-tumor activity alone and in combination with anti-PD-1 and anti-PD-L1
Authors: S. Willingham, P. Ho, R. Leone, C. Choy, J. Powell, I. McCaffery, R. Miller
Journal: Annals of Oncology (2016)
TMIC-17. SUBTYPE-SPECIFIC CELLULAR COMPOSITION OF THE GLIOBLASTOMA MICROENVIRONMENT
Authors: Ioannis Kaffes, Frank Szulzewsky, Kristina Alikhanyan, Cameron Herting, Jennifer Shelton, Lene Uhrbom, Karin Forsberg Nilsson, Sven Nelander, Bengt Westermark, Jason Huse, Eric Holland, Daniel Brat, Dolores Hambardzumyan
Journal: Neuro-Oncology (2016)

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor, which has a dismal prognosis in spite of an aggressive, multi-modal treatment regimen. The Cancer Genome Atlas has identified four major subtypes based on distinct genetic signatures. These subtypes are referred to as proneural, neural, mesenchymal, and classical based on their associations with diverse neural cell lineages. The mesenchymal subtype, for example, shows enrichment of immune response-related genes and an association with tumor-associated macrophages (TAMs). TAMs have been shown to promote GBM growth and progression and, along with other non-neoplastic cells, they constitute integral elements of the GBM microenvironment. In light of the molecular heterogeneity among the distinct subgroups, we postulated corresponding subtype-specific differences in the cellular composition of the associated microenvironment. In order to test this hypothesis, immunohistochemical analysis of the proneural, classical, and mesenchymal subtypes was performed in order to identify various non-neoplastic cell populations and their relative abundance. Human data were validated using genetically engineered mouse models of proneural and mesenchymal GBM. Quantification of immunohistochemical staining for distinct markers revealed an increased infiltration of immune cells, including TAMs and CD8-positive T cells, in the mesenchymal subtype in both human and mouse. Furthermore, TAM-positive area positively correlated with CD8-positive and FoxP3-positive T cells when analyzed for all GBM.These findings provide evidence for microenvironmental heterogeneity underlying distinct GBM subtypes and highlight the need for evaluating its functional consequences using mouse models. A more comprehensive understanding of the subtype-specific differences in microenvironmental signals will aid in the design of novel stroma-targeted therapies for GBM.
Pooled Multi-Trial Analysis of Venetoclax Efficacy in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia
Authors: Andrew W. Roberts, John F Seymour, Barbara Eichhorst, Stephan Stilgenbauer, Michael Y. Choi, Matthew S. Davids, John F. Gerecitano, Relja Popovic, Brenda Chyla, Ming Zhu, Maria Verdugo, Jalaja Potluri, Leanne Lash, Su Young Kim, Michael Hallek
Journal: Blood (2016)
NTOX-07. LASER INTERSTITIAL THERMAL THERAPY WITH ADJUVANT RADIOTHERAPY INDUCED CEREBRAL EDEMA IN PATIENTS WITH BRAIN TUMOR
Authors: Stefania Maraka, Karam Asmaro
Journal: Neuro-Oncology (2016)

Laser interstitial thermal therapy (LITT) is an image-guided technique that uses high temperatures to ablate pathological tissue and is commonly used for recurrent or deeply seated tumors. Some patients are also treated with adjuvant radiotherapy (RT). Our aim was to investigate whether LITT and RT in close succession to each other induced worsening symptomatic cerebral edema. We retrospectively reviewed records of patients who underwent Visualase LITT at our institution (March 2014-February 2016) and RT less than 60 days apart. MRI brain and clinical information were reviewed at three time points (pre-treatment, post-LITT, and post-RT). Data is presented as a median (range). We studied 10 patients with brain tumor; 8 glioblastoma, 1 anaplastic astrocytoma, and 1 metastasis, 6 (60%) were men, age at treatment was 61.5 (52-76) years. There were 6 cortical versus 4 subcortical tumors. The majority of patients underwent LITT followed by RT except for 2. Time interval between LITT and RT was 24 (9-43) days. Increased ablation volume post-LITT compared to pre-operatively tumor volume was seen in 9 patients with a mean enlargement of 15% overall. RT treatments included external beam fractionated radiation treatment (EBRT) (n=8), EBRT with stereotactic radiosurgery (SRS) (n=1), and fractionated SRS (n=1). Pre-treatment MRI showed cerebral edema in 9 patients. Post-LITT MRI showed worsening cerebral edema in 4 patients, 3 were symptomatic (1 had disease progression). One patient who received RT prior to LITT had asymptomatic cerebral edema post-RT that improved post-LITT. Post-RT MRI showed worsening symptomatic cerebral edema in a patient who had EBRT+SRS. Avastin was used in 1 patient and 2 patients had prolonged use of steroids (>65 days). LITT and RT treatment can induce symptomatic cerebral edema which can be effectively managed with steroids and/or Avastin. Treating physicians need to be cognizant of this risk.
Variability In Hb A2 levels among Individuals with Beta-Thalassemia Trait: Is Iron Deficiency Associated with Abnormally Low Hb A2?
Authors: Madeleine Verhovsek, Timothy O'Shea, Geoff Gibney, Jason C.C. So, Edmond ShiuKwan Ma, Li Chong Chan, Martin H. Steinberg, David H.K. Chui
Journal: Blood (2010)
PALL-06. IMPROVING PATIENT OUTCOMES THROUGH A MULTIDISCIPLINARY NEURO-ONCOLOGY REHABILITATION CLINIC
Authors: Alexander Mohler, Amy Callan, Renee Peter, Laura Palmer, Douglas Ney
Journal: Neuro-Oncology (2016)

Patients with brain tumors often exhibit significant functional deficits and have multiple rehabilitation needs. Early access to rehabilitation services may reduce morbidity particularly associated with falls. Multidisciplinary clinics have been shown to optimize health care delivery, improve survival and quality of life in patients with other chronic neurological diseases. Patients with immediate complex rehabilitation needs were identified from the Neuro-Oncology clinic. Patients were evaluated by their Neuro-Oncologist followed by a Physical Therapist and Occupational Therapist during one appointment. Patients completed the EORTC QLQ-30 and BN-20 questionnaires, the Activities-specific Balance Confidence scale (ABC) and 3-question fall risk assessment. Therapists completed the Functional Reach test (FRT) and Timed up and go test (TUG) and provided therapy and education. Patient satisfaction was assessed following each appointment. 8 patients (5 male) were seen and evaluated. Median age was 52 years (range, 34-71); 6 patients had primary brain tumors, median KPS was 75% (range, 50%-80%). Median global health status/QOL score was 67% (range, 0-83%). Median ABC scale was 28% (range, 0-70%), median TUG of 14.5s [range, 8-160s], and median FRT of 12.25in (range, 11-15in). Five patients reported a fall in the prior 3 months; 4 patients reported fear of falls; 6 patients reported difficulty ambulating. At follow-up, 1 patient reported prior fall, 3 patients reported fear and 4 patients reported difficulty ambulating. Universally, patients reported the experience as positive, convenient and helpful. This multidisciplinary approach was developed to increase timely rehabilitation services to patients with complex needs. Treated patients were highly debilitated with substantial functional deficits and reduced quality of life. Patients reported high levels of satisfaction with the intervention and felt well educated. There was a trend towards improved answers on the fall questionnaires post-intervention over time. Further evaluation investigating quality of life impact is ongoing.
Improving Children’s Access to Cancer Clinical Trials
Authors: Susan Jenks
Journal: JNCI Journal of the National Cancer Institute (2017)

treatment and cancer disease-related symptoms-such as fatigue," Theobald said."We realized the importance of using valid screening processes to make treatment of depression in cancer patients more effective.In later trials we documented that careful use of standard antidepressants is an effective way to treat this common illness.""Overall there is great hope," Theobald said."Depression associated with cancer can be treated effectively."
Transduction of Hematopoietic Stem/Progenitor Cells with a Lentivirus Expressing FANCA off the Human Phosphoglycerate Kinase Promoter Corrects the Fanconi Anemia Phenotype,
Authors: Zejin Sun, Jingling Li, Yanzhu Yang, Yan Li, Dirk Lindemann, Feng-chun Yang, D. Wade Clapp, Helmut Hanenberg
Journal: Blood (2011)
Comprehensive genomic profiles of metastatic and relapsed salivary gland carcinomas are associated with tumor type and reveal new routes to targeted therapies
Authors: J.S. Ross, L.M. Gay, K. Wang, J.A. Vergilio, J. Suh, S. Ramkissoon, H. Somerset, J.M. Johnson, J. Russell, S. Ali, A.B. Schrock, D. Fabrizio, G. Frampton, V. Miller, P.J. Stephens, J.A. Elvin, D.W. Bowles
Journal: Annals of Oncology (2017)

Relapsed/metastatic salivary gland carcinomas (SGCs) have a wide diversity of histologic subtypes associated with variable clinical aggressiveness and response to local and systemic therapies. We queried whether comprehensive genomic profiling could define the tumor subtypes and uncover clinically relevant genomic alterations, revealing new routes to targeted therapies for patients with relapsed and metastatic disease.From a series of 85 686 clinical cases, DNA was extracted from 40 µm of formalin-fixed paraffin embedded (FFPE) sections for 623 consecutive SGC. CGP was carried out on hybridization-captured, adaptor ligation-based libraries (mean coverage depth, >500×) for up to 315 cancer-related genes. Tumor mutational burden was determined on 1.1 Mb of sequenced DNA. All classes of alterations, base substitutions, short insertions/deletions, copy number changes, and rearrangements/fusions were determined simultaneously.The clinically more indolent SGC including adenoid cystic carcinoma, acinic cell carcinoma, polymorphous low-grade adenocarcinoma, mammary analog secretory carcinoma, and epithelial-myoepithelial carcinomas have significantly fewer genomic alterations, TP53 mutations, and lower tumor mutational burden than the typically more aggressive SGCs including mucoepidermoid carcinoma, salivary duct carcinoma, adenocarcinoma, not otherwise specified, carcinoma NOS, and carcinoma ex pleomorphic adenoma. The more aggressive SGCs are commonly driven by ERBB2 PI3K pathway genomic alterations. Additional targetable GAs are frequently seen.Genomic profiling of SGCs demonstrates important differences between traditionally indolent and aggressive cancers. These differences may provide therapeutic options in the future.
Updated results from a phase I study of nivolumab (Nivo) in combination with ipilimumab (Ipi) in metastatic renal cell carcinoma (mRCC): The CheckMate 016 study
Authors: H. Hammers, E.R. Plimack, J.R. Infante, B.I. Rini, D. McDermott, L. Lewis, M.H. Voss, P. Sharma, S.K. Pal, A. Razak, C.K. Kollmannsberger, D. Heng, J. Spratlin, B. McHenry, P. Gagnier, A. Amin
Journal: Annals of Oncology (2016)
Characterization of familial Waldenstrom's Macroglobulinemia
Authors: R. Manning, A. R. Branagan, Z. Hunter, O. Tournilhac, D. D. Santos, S. P. Treon
Journal: Journal of Clinical Oncology (2004)

6558 Background: Waldenstrom's macroglobulinemia (WM) is a B-cell malignancy, recently defined by a consensus panel as represented by the WHO/REAL pathological diagnosis of IgM secreting lymphoplasmacytic lymphoma (Semin Oncology 30:110, 2003). Previous reports have suggested the existence of familial cases of WM, though the frequency, as well as clinical and laboratory features between patients with and without a familial history remains to be defined. Methods: Medical records and laboratories for 181 patients presenting with the consensus panel defined diagnosis of WM were reviewed. Conventional G-banding and M-FISH studies of bone marrow (BM) specimens were performed for 33 of these patients (13 familial and 20 non-familial), and demonstrated 6q deletions in 4 patients as the only recurrent abnormality. BAC FISH analysis was then performed on BM samples utilizing multiple probes for chromosome 6 including RP11–91c23 and RP11–171J20 (Children's Hospital Oakland Research) which hybridize to 6q21–22. Results: We observed that 36 of 181 (20%) patients with the consensus panel defined diagnosis of WM had at least one first degree relative with either WM (n=14), or a related B-cell disorder: Multiple Myeloma (n=7); Non-Hodgkin's lymphoma (n=5); Monoclonal Gammopathy of Unknown Significance (n=3); Acute Lymphocytic Leukemia (n=3); Chronic Lymphocytic Leukemia (n=2) and Hodgkin's disease (n=2). No significant differences at presentation in age, serum IgM, bone marrow involvement by tumor cells, complete blood counts, IgG and IgA, serum viscosity, and B2M levels were found between patients with and without a familial background. Moreover, BM cytogenetic and M-FISH studies demonstrated no differences between familial an non-familial WM patients, whilst BAC FISH analysis demonstrated similar levels of 6q21–22 deletions (92.3% and 95%, respectively) among patients with, or without a familial background. Conclusions: Despite the common presentation of WM with a familial history of WM or a closely related B-cell malignancy, no significant differences in clinical, laboratory, and cytogenetic features were found between patients with and without a familial background. No significant financial relationships to disclose.
Molecular Mechanism Of Regulation Of Extramedullary Infiltration In AML1/ETO Positive Acute Myeloid Leukemia By APP/ERK/MMP-2
Authors: Guopan Yu, Fan Yi Meng, Ling Jiang, Changxin Yin, Zhixiang Wang, Hongsheng Zhou, Xuejie Jiang, Lingxiu Zhang, Rui Cao, Libin Liao
Journal: Blood (2013)
NIMG-43. APPLICATION OF AN ADVANCED DIFFUSION-WEIGHTED MRI TECHNIQUE TO CHARACTERIZE GLIOMA MICROSTRUCTURE AND RELATIONSHIP TO HISTOPATHOLOGY
Authors: Prasanna Parvathaneni, Joanna Phillips, Juan R Cabrera, Anny Shai, Soonmee Cha, Susan Chang, Sarah Nelson, Janine Lupo
Journal: Neuro-Oncology (2016)

Diffusion-weighted MRI techniques have shown great potential in evaluating tumor cellularity and response to therapy. However, recent advances in diffusion models such as NODDI that probe underlying tissue microstructure in normal brain have not been compared to histopathological findings in patients with brain tumors. The goal of this study was to evaluate the relationship between intracellular volume fraction (Vic), a measure of tissue microstructure derived from the NODDI diffusion model, and histopathological features of glioma compared to that of the standard Apparent Diffusion Coefficient (ADC) metric calculated from diffusion tensor imaging (DTI). A total of 92 image-guided tissue samples from 29 patients with astrocytic gliomas were analyzed. Imaging data included two-shell diffusion-weighted imaging data (24 gradient directions, b=1000 s/mm2 and 55 directions, b=2000 s/mm2) and standard anatomical imaging. Histopathological analysis of acquired tissue samples included tumor grade, tumor score, cellularity, microvascular hyperplasia (MVH), and Ki67. While ADC and Vic were both significantly correlated with cellularity in contrast-enhancing tissue samples from patients with GBM (p<0.05; Spearman rank correlation), only Vic from the NODDI model was associated with tumor score (p<0.002, ordinal logistic regression). Vic values were also significantly different between tissue samples with tumor scores of 2 and 3, while ADC values differentiated tumor scores of 0 and 1 (all p<0.05, Wilcoxon rank-sum). When including all tumor grades, both ADC and Vic, were correlated with Ki67 (p<0.005 ADC, p<0.00001 Vic; Spearman rank correlation) and associated with MVH (p<0.001 ADC, p<0.0001 Vic; ordinal logistic regression). Our initial results suggest that NODDI parameters may be more specific to aggressive tumor microstructure in GBM and complement conventional DTI metrics in identifying active tumor. Current analyses are evaluating the relationship between these metrics and molecular markers related to outcome in order to explore the prognostic value of these new diffusion metrics.
Circulating Endothelial Cells and Circulating Endothelial Progenitor Cells in Polycythemia Vera.
Authors: Rasmus T. Hoeg, Dean A. Jobe, Krista E. Asp, Steven M. Callister, Lori A. Meyer, Michelle A. Mathiason, Craig E. Cole, Wayne A. Bottner, John P. Farnen, Ronald S. Go
Journal: Blood (2006)
Donor Lymphocyte Transfusion (DLT) in the Treatment of Relapsed CML after Allogeneic PBSCT - A Retrospective Analysis of 346 Patients by the EBMT Chronic Leukemia Working Party.
Authors: Christoph Schmid, Anja v. Biezen, Kimmo Porkka, Yves Chalandon, Alvaro Urbano, Eduardo Olavarria, Theo de Witte, Bernd Hertenstein, Wiliam Archese, Richard Clark, Hans-Jochem Kolb, Dietger Niederwieser, Cesare Guglielmi
Journal: Blood (2005)
Can irinotecan dose reduction according to ugt1a1 genotype avoid severe toxicities?
Authors: F. Daniel, L. Belluomini, F. Lancia, L. Martella, I. Toma, A. Moretti, E. Bannò, I. Carandina, M. Marzola, M. Fabbri, A. Frassoldati
Journal: Annals of Oncology (2016)
Randomized phase II study of S-1 and concurrent radiotherapy with versus without induction chemotherapy of gemcitabine for locally advanced pancreatic cancer (LAPC): Final analysis of JCOG1106
Authors: T. Ioka, A. Fukutomi, J. Mizusawa, H. Katayama, S. Nakamura, Y. Ito, N. Hiraoka, M. Ueno, M. Ikeda, K. Sugimori, K. Shimizu, T. Okusaka, M. Ozaka, H. Yanagimoto, S. Nakamori, T. Azuma, A. Hosokawa, N. Sata, T. Mine, J. Furuse
Journal: Annals of Oncology (2016)
Treatment of Post-transplant Complex Airway Stenosis with a Three-Dimensional, Computer-assisted Customized Airway Stent
Authors: Nicolas Guibert, Alain Didier, Benjamin Moreno, Laurent Mhanna, Laurent Brouchet, Gavin Plat, Christophe Hermant, Julien Mazieres
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Prevalence of molecular subtypes and prognosis of invasive breast cancer in Moroccan patients (Fez region): Experience of Hassan II University Hospital.
Authors: O. El Mesbahi, Y. Akasbi, F. Abbass, S. Bennis, K. Znati, A. Amarti
Journal: Journal of Clinical Oncology (2011)

e11054 Background: The most interesting study to classify breast cancers was the one realized by Carey et al. They created updated immunohistochemical subtype definitions: luminal A (ER positive (ER+) and/or PR positive (PR+), Her2 negative (Her2-)), luminal B (ER+ and/or PR+, Her2 positive (Her2+), Her2+/ER− subtype (Her2+, ER−, PR−), basal-like (ER−, PR−, Her2−, cytokeratin (CK) 5/6+ and/or Her1+) and unclassified subtype (ER-,PR-, Her2-, Her1- and CK5/6-). The aim of our study was to estimate the prevalence of breast cancer subtypes in Moroccan patients, to establish the correlation between clinico-pathological characteristics and survival (disease-free survival (DFS) and overall survival (OS)). Methods: We reviewed 366 cases of breast cancer diagnosed between January 2007 to June 2010 at the Department of pathology. Age, size tumour, metastatic profile, ganglionnar profile, OS and DFS were analysed on 181 patients. These last were estimated by Kaplan-Meier analysis and a log-rank test to estimate outcome differences among subgroups. Results: The average size of tumors was 3,7±2,6 cm ,the histological grade distributions were 54,7% grade II, 30,7% were grade III but only 14,6% were grade I. The immunohistochemical study show that 196 tumors (53,6%) were classified as luminal A, 60 (16,4%) as luminal B, 46 (12,6%) as Her2-overexpressing, 46 (12,6%) as basal-like, and 18 (4,9%) as unclassified. The Kaplan–Meier curves showed a significant difference in OS at 3-years between the subtypes (P= 0,042), with the triple negative subtype associated with the lowest survival probability (49%), but the luminal A was associated with the best survival probability (88%) compared to those in the other subtypes (77% for luminal B, 75% for Her2-overexpressing). These subtypes also differed significantly in 3-years DFS (p=0.002): luminal A (59%), luminal B (41%), triple negative (39%), and Her2-overexpressing (38%). Conclusions: We have shown that simple IHC-based categorization of breast tumors can be helpful. This information can be used toward improved therapeutic decisions. The findings highlight the importance of early detection by clinical and mammographic methods.
Measles in older children and adults
Authors: Beatrice Clare Cockbain, Tehmina Bharucha, Dianne Irish, Michael Jacobs
Journal: BMJ (2017)

#### What you need to know

A 23 year old woman has fever, flu-like symptoms, diarrhoea, and a rash that has spread from her face to her body. She cannot recall being in contact with anyone unwell and has not recently travelled or taken any drugs. She reports missing vaccinations as a child because her parents were concerned about safety. On examination she has a maculopapular blanching rash on her face and chest. Measles was suspected and confirmed with serology that was positive for immunoglobulin M antibodies to the measles virus. Reverse transcription polymerase chain reaction on a throat swab detected measles virus RNA.

Measles is widely perceived as a disease of early childhood, despite almost two thirds of recent cases in the United Kingdom being in those aged 15 and older.1 Patients typically present with fever, cough, coryza, and conjunctivitis, followed two to four days later by a characteristic erythematous maculopapular rash that spreads downwards from the face (figs 1⇓ and 2⇓).2 Patients are infectious from four days before to four days after the onset of rash. Koplik’s spots—whitish lesions …
Pharmacogenomic predictors of cisplatin oto- and nephrotoxicity in head and neck cancer patients treated with chemoradiation
Authors: E. Winquist, W.A. Teft, A. Nichols, C. Parker, M. Trinnear, P. Francis, N. Bukhari, J. Lukovic, Y.-H. Choi, S. Kuruvilla, S. Richter, A. Hammond, D. Macneil, N. Read, K. Fung, V. Venkatesan, S. Welch, D. Palma, J. Yoo, R.B. Kim
Journal: Annals of Oncology (2016)