tbuckley/cabot-search huggingface dataset:
Successful Emulation of IV Decitabine Pharmacokinetics with an Oral Fixed-Dose Combination of the Oral Cytidine Deaminase Inhibitor (CDAi) E7727 with Oral Decitabine, in Subjects with Myelodysplastic Syndromes (MDS): Final Data of Phase 1 Study
Authors: Guillermo Garcia-Manero, Olatoyosi Odenike, Philip C. Amrein, David P. Steensma, Amy E. DeZern, Laura C. Michaelis, Stefan Faderl, Hagop M. Kantarjian, James N. Lowder, Pietro Taverna, Aram Oganesian, Xiaoping Zhang, Mohammad Azab, Michael R. Savona
Journal: Blood (2016)
Prospective Evaluation of Laboratory Tests for the Diagnosis of Heparin-Induced Thrombocytopenia.
Authors: John L. Francis, Alane Drexler, Mary Kathryn Duncan, Hina Desai, Mildred Amaya, Theresa Robson, Todd V. Meyer, Edward Reyes, Kristin Rathmann, Ali Amirkhosravi
Journal: Blood (2006)
A Phase II Study of the Purine Nucleoside Phosphorylase (PNP) Inhibitor RO5092888 (BCX-4208) in Patients with Moderate to Severe Chronic Plaque Psoriasis: Safety, Tolerability and Lymphocyte Effects
Authors: Joseph P Gomes, Angela Georgy, Sharon Passe, Adrienne Farid, Shanta Bantia, Gerhard Wolff
Journal: Blood (2008)
Tolerance profile for cow milk allergy
Authors: Paula Quadros Marques, Mariele Morandin Lopes, Pâmella Diogo Salles, Claudia Leiko Yonekura Anagusko, Larissa Prando Cau, Danilo Gois Goncalves, Ariana Campos Yang
Journal: Journal of Allergy and Clinical Immunology (2017)
Epstein–Barr virus-associated gastric cancer reveals intratumoral heterogeneity of PIK3CA mutations
Authors: C. Böger, S. Krüger, H.M. Behrens, S. Bock, J. Haag, H. Kalthoff, C. Röcken
Journal: Annals of Oncology (2017)

Recent whole-genome sequencing identified four molecular subtypes of gastric cancer (GC), of which the subgroup of Epstein-Barr virus-associated GC (EBVaGC) showed a significant enrichment of PIK3CA mutations. We here aimed to validate independently the enrichment of PIK3CA mutations in EBVaGC of a Central European GC cohort, to correlate EBV status with clinico-pathological patient characteristics and to test for a major issue of GC, intratumoral heterogeneity.In a first step, 484 GCs were screened for EBV and PIK3CA hot spot mutations of exon 9/20 using EBER in situ hybridization and pyrosequencing, respectively. Secondly, an extended sequencing of PIK3CA also utilizing next generation sequencing was carried out in all EBVaGCs and 96 corresponding lymph node metastases.Twenty-two GCs were EBER-positive, all being of latency type I. Intratumoral heterogeneity of EBER-positivity was found in 18% of EBVaGCs. Twenty-three GCs held PIK3CA mutations in hot spot regions of exon 9 or 20, being significantly more common in EBVaGCs (P < 0.001). Subsequent extended sequencing of PIK3CA of EBVaGCs showed that 14% harvested three to five different PIK3CA genotypes (including wildtype) in the same primary tumor, albeit in histologically and spatially distinct tumor areas, and that intratumoral heterogeneity of PIK3CA was also present in the corresponding lymph node metastases.Our findings unravel issues of tumor heterogeneity and illustrate that the assessment of the EBV status in tissue biopsies might carry the risk of sampling errors, which may significantly hamper adequate molecular tumor classification in a more clinical setting. Moreover, this is the first report of intratumoral heterogeneity of PIK3CA mutations in GC, and our findings lead to the conclusion that PIK3CA mutant and -wildtype tumor subclones are skilled to metastasize independently to different regional lymph nodes.
Early Response Using Serum Immunoglobulin Free Light Chain (sFLC) Measurement Predicts Response to Therapy in Waldenstrom Macroglobulinemia (WM)
Authors: Xavier Leleu, Aldo M. Roccaro, Renee Leduc, Stephanie Poulain, Anne-Sophie Moreau, Julie Gay, Remy Dulery, Paul G. Richardson, Irene M. Ghobrial
Journal: Blood (2008)
IMST-56. TUMOR LYSATE-PULSED DC VACCINATION INDUCES NEOANTIGEN-SPECIFIC T CELL RESPONSES
Authors: Richard Everson, Namjo Shin, Joseph Antonios, Horacio Soto, Alexander Tucker, Jesse Zaretsky, Joey Orpilla, Sue Rathe, Flavia Popescu, Davd Largaespada, Linda Liau, Robert Prins
Journal: Neuro-Oncology (2016)

Dendritic cell (DC) vaccines currently in phase III trials for glioblastoma use autologous tumor lysate (ATL) as an antigen source to induce a lymphocytic infiltration but it remains unclear what epitopes this immune response is specifically directed against. We hypothesized that the most immunologically relevant target antigens in the ATL are neoantigen peptides arising from tumor-specific mutations. To test this, we identified non-synonymous coding mutations in the GL261 murine glioma cell line and human GBM samples using whole exome seq, RNAseq, and bioinformatics software to predict the mutated sequences which result in enhanced peptide-MHC binding. Nine candidate neoantigens were identified from the GL261 glioma line. Mice bearing intracranial GL261 gliomas were vaccinated with control, ATL, or neoantigen-pulsed DC vaccination. Tumor-infiltrating lymphocytes (TILs) were isolated and co-cultured with DCs pulsed with peptides containing the neoantigen sequences for flow cytometry. 5x105 -2x106 TILs were recovered from vaccine-treated animals, whereas <105 were recovered from controls, indicating a enhanced T cell infiltration due to the vaccine.Ex vivo restimulation induced CD69 upregulation in 0, 21, and 26% of TILs in control, ATL, and neoantigen-pulsed DC vax treatment groups, respectively. Survival was significantly extended similarly in both ATL and neoantigen-pulsed DC vax treatment groups compared with control treatment (P<0.02). In human GBM patients, we identified an average of 15 strong binding and 9 weak binding neoantigens per tumor from 8 patients treated with ATL DC vaccination. TCR sequencing from the original tumor and TIL cultures revealed common high-frequency TCR clonotypes. Together, these studies indicate that tumor lysate DC vaccines are capable of priming CD8+ T cell responses directed at tumor-specific mutations in mice. Further studies are underway to characterize the immune responses to these candidate neoantigens in human patients following ATL-pulsed DC Therapy.
Effect of Radiotherapy on Painful Bone Metastases
Authors: Rachel McDonald, Keyue Ding, Michael Brundage, Ralph M. Meyer, Abdenour Nabid, Pierre Chabot, Genevieve Coulombe, Shahida Ahmed, Joda Kuk, A. Rashid Dar, Aamer Mahmud, Alysa Fairchild, Carolyn F. Wilson, Jackson S. Y. Wu, Kristopher Dennis, Carlo DeAngelis, Rebecca K. S. Wong, Liting Zhu, Stephanie Chan, Edward Chow
Journal: JAMA Oncology (2017)

Many studies that found improved quality of life (QOL) after radiotherapy of bone metastases have small sample sizes and do not use specific questionnaires. How soon after radiotherapy one can expect an improvement in QOL is unknown.To investigate QOL at days 10 and 42 after radiotherapy with a bone metastases-specific QOL tool.In this secondary analysis of the NCIC Clinical Trials Group Symptom Control Trial SC.23, a double-blind randomized clinical trial that investigated dexamethasone for the prophylaxis of pain flare after radiotherapy, patients were accrued from 23 Canadian centers from May 30, 2011, to December 11, 2014, and were followed up for 42 days after treatment. Participants referred for radiotherapy for bone metastases were required to have a pain score at the site(s) of treatment of at least 2 (range, 0-10).Patients were treated with a single 8-Gy radiotherapy dose for 1 or 2 bone metastases.Patients reported their worst pain score and analgesic intake at baseline and days 10 and 42 after treatment. Pain response was assessed with International Bone Metastases Consensus Endpoint Definitions. Self-reported QOL was completed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Bone Metastases Module (QLQ-BM22) and the European Organisation for Research and Treatment of Cancer Quality of Life Core 15 Palliative (QLQ-C15-PAL) at the same time points.A total of 298 patients were accrued (median age, 68.8 [range, 32-94] years at day 10 and 68.0 [range, 34-90] years at day 42). A total of 122 patients (40.9%) responded to radiotherapy at day 10 and 116 patients (38.9%) at day 42. At day 10, compared with nonresponders, patients with a pain response had a greater reduction in pain (mean reduction, 17.0 vs 1.8; P = .002) and pain characteristics (mean reduction, 12.8 vs 1.1; P = .002), as well as greater improvements in functional interference (mean increase, 11.6 vs 3.6; P = .01) and psychosocial aspects (mean increase, 1.2 points in responders vs mean decrease of 2.2 points in nonresponders, P = .04). Comparing changes in QOL from baseline to day 42, responders had significantly greater improvements in the physical (mean increase, 6.2 vs -9.0; P < .001), emotional (mean increase, 12.3 vs -5.5; P < .001), and global domains (mean increase, 10.3 vs -4.5; P < .001) of the QLQ-C15-PAL compared with nonresponders.Forty percent of patients experienced pain reduction and better QOL at day 10 after radiotherapy with further improvements in QOL at day 42 in responders. A single 8-Gy radiotherapy dose for bone metastases should be offered to all patients, even those with poor survival.clinicaltrials.gov Identifier: NCT01248585.
Peach Tree Pollen As An Inhalant Allergen In A High Exposed Population
Authors: Maria Luisa Somoza, Natalia Blanca-Lopez, Natalia I. Perez-Sanchez, J Damian Lopez, Laura Victorio, Nuria Fernandez Alargunsoro, Lucia Jimeno, Gabriela Canto, Miguel Blanca, Jose Antonio Cornejo
Journal: Journal of Allergy and Clinical Immunology (2017)
TMOD-35. PRIMARY AND RECURRENT SACRAL CHORDOMA AFFECTS THE HIND LIMBS MOTOR AND NOCICEPTIVE FUNCTION IN RATS: AN ORTHOTOPIC SPINE MODEL
Authors: Rachel Sarabia-Estrada, Alejandro Ruiz-Valls, Sagar R Sha, Hugo Guerrero-Cazares, Ismael Jimenez-Estrada, Betty Tyler, Gary Gallia, Ziya Gokaslan, Alfredo Quinones-Hinojosa, Daniel Sciubba
Journal: Neuro-Oncology (2016)

Chordoma (CHO) is a slow-growing, malignant, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy. It presents high local recurrence after surgical resection. There are no animal models of spinal chordoma. 34 immunocompromised rats were engrafted in the lumbar spine with human CHO tumors: UCH1 (n=11), JHC7 (n=11), sham (n=6), and 6 intact rats were used as control groups. Rats’ neurological impairment due to tumor growth was evaluated using open field, and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. microCT, MRI and NanoScan PET/CT were performed to evaluate bone changes due to tumor growth. At D550 rats were euthanized and spines were processed for H&E and IHC for brachyury, S100B and cytokeratin. Spine tumors showed the typical CHO morphology, with positive immunoreactivity to Brachyury, S100 B, and cytokeratine. CT showed sclerotic bone lesions in CHO groups. MRI with contrast media confirmed tumor growth. UCH1group showed large tumors growing from the vertebral body invading the abdominal cavity. JHC7 group showed new bone formation and smaller tumors confined to the bone periphery. In locomotion, there was an increase in the step length and duration of the gait of tumor rats. There was a reduction in the distance traveled and speed of tumor rats in the open field test. Nociceptive response to a mechanical stimulus showed a significant increase in the paw withdrawal threshold, but the paw withdrawal response to a thermal stimulus decreased significantly in tumor-engrafted rats. We have developed an orthotopic human chordoma model in rats that reproduces cardinal clinical signs of the human pathology. Such signs include locomotor and sensory deficits present in human patients. The use of a reliable animal model of CHO will be essential for pathophysiology research and the development of new therapeutic strategies.
Breathlessness and abdominal swelling: a classic eponymous syndrome
Authors: Jennifer Kahan, Russell Banner, Kerryn Lutchman-Singh
Journal: BMJ (2017)

A previously well 50 year old woman developed shortness of breath over several weeks accompanied by abdominal distension and discomfort. She was unable to lie flat due to orthopnoea. She had no comorbidities and was on no medication. A computed tomography (CT) scan of the chest, abdomen, and pelvis was undertaken, followed by biopsy and definitive surgical treatment. Postoperative histology confirmed a benign neoplasia. What are the three main radiological findings seen in the CT image (fig 1⇓) and what is the eponymous diagnosis associated with this classic triad?



Fig 1  Coronal computed tomography (CT) image of the chest, abdomen, and pelvis



The CT shows a large right …
ACTR-19. BASELINE PLASMA MATRIX METALLOPROTEINASE 9 (MMP9) PREDICTS OVERALL SURVIVAL (OS) BENEFIT FROM BEVACIZUMAB INDEPENDENTLY OF MOLECULAR SUBTYPES IN NEWLY DIAGNOSED GLIOBLASTOMA: RETROSPECTIVE ANALYSIS OF AVAglio
Authors: Olivier Chinot, Josep Garcia, Sylvie Romain, Cedric Revil, Timothy Cloughesy, Warren Mason, Ryo Nishikawa, Roger Henriksson, Frank Saran, Antoine F. Carpentier, Khê Hoang-Xuan, Petr Kavan, Dana M. Cernea, Alba A. Brandes, Yannick Kerloeguen, Christoph Mancao, L’Houcine Ouafik, Lauren Abrey, Wolfgang Wick, Emeline Tabouret
Journal: Neuro-Oncology (2016)

Addition of bevacizumab to radiotherapy/temozolomide (RT/TMZ) improved progression-free survival (PFS) (vs placebo+RT/TMZ) but not OS in newly diagnosed glioblastoma (AVAglio/NCT00943826). However, a retrospective analysis of AVAglio suggested that patients with proneural glioblastoma derived an OS benefit from first-line bevacizumab. In recurrent glioblastoma, MMP9 and MMP2 plasma levels may predict bevacizumab activity. We retrospectively analyzed AVAglio data to examine whether MMP9/MMP2 baseline plasma levels predicted OS benefit from bevacizumab in newly diagnosed glioblastoma and potential relationships between MMP and glioblastoma molecular subtypes. MMP9 and MMP2 levels were assessed (ELISA; R&D Systems) in baseline plasma samples from 577/921 patients (AVAglio: placebo n=294/bevacizumab n=283). Molecular subtypes were analyzed by gene expression profiling (placebo n=167/bevacizumab n=164). Post-hoc analysis and PFS/OS multivariate models, including MMP9/2-treatment interactions, were performed. MMP9 distribution at baseline was comparable between arms (median: placebo 82.4ng/mL [range 5–3454]; bevacizumab 83.6ng/mL [range 10–3070]). Patient characteristics were generally balanced between subgroups (per quartile [Q]), including for known prognostic factors. Patients with low MMP9 (<Q1) derived a significant 5.2-month OS benefit with bevacizumab (HR 0.51, 95% CI 0.34−0.76, p=0.0009; median 13.6 [placebo] vs 18.8 [bevacizumab] months). A consistent 5.8-month PFS benefit was seen (HR 0.36, 95% CI 0.24−0.54, pQ3), OS favored the placebo arm (HR 1.21, 95% CI 0.80−1.81) although no statistically significant difference could be shown. Molecular subtype distribution (proneural/mesenchymal/proliferative) was similar in low (Q3) MMP9 subgroups (both arms). In the multivariate analysis, an interaction was seen between treatment and MMP9 (p=0.03) for OS. Predictive value of MMP2 levels could not be shown in this study. This post-hoc analysis suggests that baseline MMP9 levels were predictive of OS benefit from bevacizumab in newly diagnosed glioblastoma; no relationship between this predictive value and molecular subtype could be shown.
SURG-05. NATIONAL TRENDS FOR REOPERATION IN PATIENTS WITH GLIOBLASTOMA MULTIFORME
Authors: Yi-Ren Chen, Jon Sole, Beatrice Ugiliweneza, Max Boakye, Stephen Skirboll
Journal: Neuro-Oncology (2016)

Despite multimodal therapies extending patient survival, Glioblastoma multiforme (GBM) recurrence is all but a certainty. To date, there have only been a few single-center studies looking at reoperations. Our study aimed to assess GBM reoperation trends nationally, with emphasis on outcomes. The linked Surveillance, Epidemiology, and End Results (SEER) – Medicare database was searched to identify patients 66 years and older with GBM from 1997-2010. The primary outcome was survival after diagnosis. Kaplan-Meier curves and multivariate analysis with the proportional hazard ratios were used. A total of 3,784 patients with recurrent GBM were identified. At the time of initial diagnosis, 341 patients (9%) underwent a biopsy as the first surgery, and 3,443 patients (91%) received a gross total resection. Reoperation - whether after an initial biopsy or resection - increased survival in patients, with a median survival of 5 months in the group that did not receive reoperation vs. 11 months in the group that did (p<.0001). Reoperated patients that underwent biopsy as the initial surgery had a median survival of 3 months without reoperation and 8 months with (P=<0.0001). In contrast, patients that underwent resection at the initial surgery had a median survival of 5 months without reoperation and 13 months with (P= <0.0001). Within the reoperated cohort, extent of the initial surgery differentially affected survival, with gross total resection appearing to improve median survival (HR 0.794, 0.731-0.962) compared to partial resection (1.033) and all other less complete resections (1.072) correlated. No statistically significant difference in survival was observed across geographic regions or academic versus private hospitals. Though definitive conclusions cannot be made given the lack of granularity, our study does support gross total resection as the initial treatment of choice for GBM, followed by reoperation, if tolerated, at the time of recurrence.
Erratum: Polymorphisms in xenobiotic transporters ABCB1, ABCG2, ABCC2, ABCC1, ABCC3 and multiple myeloma risk: a case—control study in the context of the International Multiple Myeloma rESEarch (IMMEnSE) consortium
Authors: A Martino, D Campa, G Buda, J Sainz, R García-Sanz, K Jamroziak, R M Reis, N Weinhold, M Jurado, R Ríos, Z Szemraj-Rogucka, H Marques, J Szemraj, A Stein, R Kumar, E Orciuolo, F Gemignani, S Landi, H Goldschmidt, M Petrini, C Dumontet, F Canzian, A M Rossi
Journal: Leukemia (2013)
Collaborative Innovations to Medical Global “Crowd” Rounds – An Effective Modified EdX to Complex Patient Care, Academic Learning and Global Inclusion
Authors: Lenora Mendoza Noroski, Kristin H. Dillard, Lisa R. Forbes, Mark C. Stahl, Denisse Guerrero, Luis Alberto Pedroza, Mehtap Abul, Hasibe Artac, Arnaldo L. Capriles Hulett, Saul Lugo Reyes, Francisco Espinosa
Journal: Journal of Allergy and Clinical Immunology (2017)
Release of Procoagulant and Proinflammatory Cell-Derived Microparticles (MP) During Blood Storage: Effects of Storage Time, Leukoreduction, and Residual Platelets,
Authors: Wenche Jy, Sherry Shariatmadar, Marco Ricci, Orlando Gomez-Marin, Carlos Bidot, Max E Johansen, John Morgan, Lawrence L Horstman, Yeon S Ahn
Journal: Blood (2011)
Berberine-induced bioactive metabolites of the gut microbiota improve energy metabolism
Authors: Yan Wang, Jia-Wen Shou, Xiao-Yang Li, Zhen-Xiong Zhao, Jie Fu, Chi-Yu He, Ru Feng, Chao Ma, Bao-Ying Wen, Fang Guo, Xin-Yi Yang, Yan-Xing Han, Lu-Lu Wang, Qian Tong, Xue-Fu You, Yuan Lin, Wei-Jia Kong, Shu-Yi Si, Jian-Dong Jiang
Journal: Metabolism (2017)
Histopathological response to neoadjuvant chemotherapy is predictive for prognosis in locally advanced gastroesophageal cancer
Authors: S. Spoerl, S.-E. Al-Batran, M. Feith, F. Lordick, P. Thuss-Patience, C. Pauligk, B. Haller, A. Novotny, S. Lorenzen
Journal: Annals of Oncology (2016)
Variation among follow-up survivorship guidelines for adolescent and young adults (AYA).
Authors: Erin Marie Barthel, Elizabeth Kiernan, Darcy Banco, Katherine Spencer, Susan K. Parsons
Journal: Journal of Clinical Oncology (2016)

147 Background: The AYA population is a growing group of survivors, exceeding more than 600,000 who are at high risk for late effects of cancer-directed therapy. While many guidelines exist for cancer survivorship care, choosing which to use for an AYA cancer survivor is challenging, yet essential, to ensure comprehensive follow-up care. Methods: Survivorship care plans, including treatment summaries and follow-up care plans, were created for three clinical vignettes (acute lymphoblastic leukemia, osteosarcoma, and Hodgkin Lymphoma). Four sets of guidelines were used including the Children’s Oncology Group Long-Term Follow-Up Guidelines (COG LTFU), National Comprehensive Cancer Network (NCCN) Guidelines for Age- Related Recommendations: AYA Oncology (NCCN-AYA), NCCN Guidelines for Treatment of Cancer by Site (NCCN-Site), and NCCN Guidelines for Supportive Care: Survivorship (NCCN-Survivor) and NCCN supplemental cancer screening guidelines. The follow-up care plans were compared across guidelines to determine the extent and nature of the similarities and differences concerning AYA survivorship care. Results: The guidelines differ widely on surveillance recommendations based on risk, test, and frequency. The COG LTFU recommends screening all individuals with a specific treatment exposure, whereas the NCCN-AYA recommends screening based on risk and the NCCN-Survivor recommends testing individuals with a positive review of systems and other health risk factors. To illustrate this, in the follow-up care plan for our Hodgkin Lymphoma case, recommended monitoring for cardiac toxicity varied from annual screening (COG LTFU) to ten year intervals (NCCN-Survivor), based on which guideline was used. Conclusions: The guidelines disagree on the link between treatment exposures and late effects, on the population to be screened, on the screening test to be used, and on the time interval of testing. This has significant implications for the long-term follow-up care an AYA survivor will receive. We highlight differences across the guidelines and offer solutions to harmonize guidelines to ensure comprehensive, quality survivorship care for this population.
Transforming Growth Factor-Beta 1 (TGF-Beta 1) Gene Polymorphisms are Associated with Atopic Asthma and Helminth Infections in an Admixed Population
Authors: Ryan Santos Costa, Camila Alexandrina Figueiredo, Mauricio Lima Barreto, Neuza Maria Alcântara-Neves, Laura Rodrigues, Álvaro Cruz, Lain Pontes-de-Carvalho, Candelaria Vergara, Nicholas M. Rafaels, Cassandra Foster, Joseph Potee, Monica Campbell, Rasika A. Mathias, Kathleen C. Barnes
Journal: Journal of Allergy and Clinical Immunology (2017)
Sequential Treatment with Reduced Intensity Allogeneic Stem Cell Transplantation and Imatinib for Chronic Myelogenous Leukemia (CML.
Authors: Richard Champlin, Shubhra Ghosh, Gloria McCormick, Borje Andersson, Marcos de Lima, Paolo Anderlini, Muzaffar Qazilbash, Sergio Giralt, Jorge Cortes
Journal: Blood (2004)