tbuckley/cabot-search huggingface dataset:
Challenging judgement of a low-positive ACPA test in the context of individuals at risk of RA
Authors: Aase Haj Hensvold, Anca I Catrina
Journal: Annals of the Rheumatic Diseases (2017)

Challenging judgement of a low-positive ACPA test in the context of individuals at risk of RA We thank Bossuyt 1 for his letter and the comments related to our previous published study. 2 We agree that the calculated test likelihood ratios for low-positive anticitrullinated protein antibody (ACPA) reflect the relative uncommonness of low-titre ACPA in prevalent rheumatoid arthritis (RA) (despite a significant association between).However, in contrast, a low-ACPA titre result in the context of testing for future incident RA might represent an intermediate stage in disease development in individuals on their way to develop RA.We have preliminary unpublished data showing a significant association between low-ACPA titre and future incident RA in our cohort.Judgement of the ACPA test results is therefore more challenging in such context and probably additional information (such as presence or absence of the human leukocyte antigen (HLA)-shared epitope risk gene alleles) will improve the discrimination of individuals who will not and those who will continue to develop high ACPA titres and eventually RA.More studies addressing the additional benefit of a higher relative weight for high titre as compared with low-ACPA titre in the context of clinical manifest RA and future RA are needed.
Lymphoma and Lactic Acidosis
Authors: John W. McKay, Dominique Delbeke, Martin P. Sandler
Journal: Clinical Nuclear Medicine (2017)

A 39-year-old man presented with new onset of sinus congestion, shortness of breath, and diaphoresis. His laboratory tests were notable for hypercalcemia and lactic acidosis. A CT scan of the head demonstrated mild paranasal disease. CT scan of the chest, abdomen, and pelvis demonstrated omental caking with lymphadenopathy and a thickened loop of bowel in the left upper quadrant suggestive of lymphoma. All abdominal lesions seen in the CT were intensely F-FDG avid with diffuse uptake in the bone marrow. There was markedly decreased F-FDG uptake in both the brain and liver. Histopathology was positive for Burkitt lymphoma.
GENT-43. EVOLUTIONARY ADVANTAGE OF PSEUDOPALISADING IN DIFFUSE HIGH-GRADE GLIOMA IS UNRELATED TO PROLIFERATION OR TP53 MUTATIONAL LOAD
Authors: Robert Macaulay, Hannah Rutherford, James Saller, Jacob Scott, David Basanta, Anthony Magliocco
Journal: Neuro-Oncology (2016)

Glioblastoma (GbM) is the most common and most lethal primary brain tumor in adults, with only marginal improvements in outcome over the past several decades. One characteristic feature of GbM is pseudopalisading necrosis (PPN). We and others have postulated that hypoxic zones in GbM which presage necrosis may exert selective pressure on cancer stem cells, altering evolutionary dynamics. For unknown reasons, hypoxic tumor sub-volumes are more radio-resistant than amply oxygenated regions. One hypothesis is that GbM cancer stem cells (CSCs) may preferentially survive relative hypoxia to form new tumor colonies. We hypothesized that PPN reflects a hyper-evolutionary state, in which daughter cells randomly acquire selectively advantageous mutations. Genes known to be mutated in GbM, such as TP53, might exhibit multiple sequence variants, which could serve as a surrogate for a hyper-evolutionary state. We assesed non-necrotic and perinecrotic regions (both PPN and non-PPN) within GbMs to investigate proliferative dynamics and genetic heterogeneity. Next generation sequencing (NGS) data for TP53 served as a surrogate marker for mutational burden. Tumors were stratified for IDH1/2 mutation status and for MGMT promoter methylation. Immunostaining for p53 was used as a surrogate for TP53 mutation on tissue sections, and Ki67 was assessed to determine regional variability in proliferation. Silencing of the DNA-repair enzyme methyl guanine methyl transferase (MGMT) through promoter methylation (pM) is postulated to impact sensitivity to adjuvant therapy; we wondered whether MGMT-pM tumors may also exhibit higher mutational loads. We observed that GbM proliferation was not elevated in perinecrotic zones, with or without pseudopalisading. TP53 was commonly mutated, but did not correlate with proliferative rates or perinecrotic zones. MGMT promoter methylation did not influence the likelihood of TP53 mutations in IDH-wt GbM. We concluded that neither the Ki-67 index nor the TP53 mutational load were informative markers of evolutionary pressure in GbM.
Uterine Cancers Clinical Practice Guidelines
Authors: Benjamin E Greer, Wui-Jin Koh, Nadeem Abu-Rustum, Michael A Bookman, Robert E Bristow, Susana Campos, Kathleen R Cho, Larry Copeland, Patricia Eifel, Wainwright Jaggernauth, Anuja Jhingran, Daniel S Kapp, John Kavanagh, Gary H Lipscomb, John R Lurain, Robert J Morgan, Subir Nag, Edward E Partridge, C Bethan Powell, Steven W Remmenga, R Kevin Reynolds, William Small, John Soper, Nelson Teng
Journal: Journal of the National Comprehensive Cancer Network (2006)

Adenocarcinoma of the endometrium is the most common malignancy of the female genital tract in the United States. Many physicians believe that adenocarcinoma of the endometrium is a relatively benign disease because of the early symptoms of irregular vaginal bleeding in this predominantly postmenopausal patient population, the often-localized nature of the disease, and the generally high survival rate. However, the estimated number of deaths from endometrial cancer continues to increase, indicating the need for a critical reassessment of the guidelines for managing endometrial cancer. Physicians must identify high-risk patients and tailor treatment appropriately to provide the best opportunity for long-term survival. For the most recent version of the guidelines, please visit NCCN.org
TMOD-26. DEVELOPING PATIENT-DERIVED XENOGRAFT MODELS OF METASTATIC CANCER TO THE BRAIN
Authors: Priya Kumthekar, Atique Ahmed, Maciej Lesniak, C. David James, Craig Horbinski
Journal: Neuro-Oncology (2016)

INHBA, a TGF-β ligand found mutated in lung adenocarcinoma, showed reduced expression in BMICs with knockdown of SPOCK1, defining a novel pathway between INHBA, SPOCK1 and TWIST2 and implicating the involvement of the TGF-β signaling pathway in BM development.Our development of a novel preclinical model of BM, through which we have identified several novel BMIC regulators, present potential therapeutic targets that could aid in blockage of the metastatic process, and transform a uniformly fatal systemic disease into a locally controlled and eminently more treatable one.
Phase 1b dose-finding study of avelumab (anti-PD-L1) + axitinib in treatment-naïve patients with advanced renal cell carcinoma
Authors: J. Larkin, B.I. Rini, P. Nathan, F. Thistlethwaite, M. Gordon, M. Martgnoni, D. Magazzu, C. Chiruzzi, A. Di Pietro, T.K. Choueiri
Journal: Annals of Oncology (2016)
Persistence of Zika Virus in Body Fluids — Final Report
Authors: Gabriela Paz-Bailey, Eli S. Rosenberg, Kate Doyle, Jorge Munoz-Jordan, Gilberto A. Santiago, Liore Klein, Janice Perez-Padilla, Freddy A. Medina, Stephen H. Waterman, Laura E. Adams, Matthew J. Lozier, Jorge Bertrán-Pasarell, Carlos Garcia Gubern, Luisa I. Alvarado, Tyler M. Sharp
Journal: New England Journal of Medicine (2017)

To estimate the frequency and duration of detectable Zika virus (ZIKV) RNA in human body fluids, we prospectively assessed a cohort of newly infected participants in Puerto Rico.We evaluated samples obtained from 150 participants (including 55 men) in whom ZIKV RNA was detected on reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay in urine or blood in an enhanced arboviral clinical surveillance site. We collected serum, urine, saliva, semen, and vaginal secretions weekly for the first month and then at 2, 4, and 6 months. All specimens were tested by means of RT-PCR, and serum was tested with the use of anti-ZIKV IgM enzyme-linked immunosorbent assay. Among the participants with ZIKV RNA in any specimen at week 4, biweekly collection continued until all specimens tested negative. We used parametric Weibull regression models to estimate the time until the loss of ZIKV RNA detection in each body fluid and reported the findings in medians and 95th percentiles.The medians and 95th percentiles for the time until the loss of ZIKV RNA detection were 14 days (95% confidence interval [CI], 11 to 17) and 54 days (95% CI, 43 to 64), respectively, in serum; 8 days (95% CI, 6 to 10) and 39 days (95% CI, 31 to 47) in urine; and 34 days (95% CI, 28 to 41) and 81 days (95% CI, 64 to 98) in semen. Few participants had detectable ZIKV RNA in saliva or vaginal secretions.The prolonged time until ZIKV RNA clearance in serum in this study may have implications for the diagnosis and prevention of ZIKV infection. Current sexual-prevention guidelines recommend that men use condoms or abstain from sex for 6 months after ZIKV exposure; in 95% of the men in this study, ZIKV RNA was cleared from semen after about 3 months. (Funded by the Centers for Disease Control and Prevention.).
Assessment of Proliferation Induced in Fibroblasts and Rabbit Corneal Epithelial Cells by a Platelet Lysate Formulation: A Stability Study
Authors: Carla Caramella, Maria Cristina Bonferoni, Silvia Rossi, Giuseppina Sandri, Sara Gibin, Cesare Perotti, Claudia Del Fante, Angelo Gallanti, Laura Salvaneschi
Journal: Blood (2008)
SURG-15. INTEGRATING MOLECULAR MARKERS AND EXTENT OF RESECTION FOR RISK STRATIFICATION OF PATIENTS WITH NEWLY-DIAGNOSED GLIOBLASTOMA: A MULTICENTRE STUDY
Authors: Wajid Sayeed, Eugene Batuyong, Haocheng Li, Magalie Cadieux, John Kelly, James Scott, Julie Semenchuk, Marshall Pitz, Jacob Easaw
Journal: Neuro-Oncology (2016)
PDTB-20. PRECLINICAL EFFICACY OF ALK2 INHIBITORS IN ACVR1 MUTANT DIPG
Authors: Diana Carvalho, Kathryn Taylor, Nagore Gene Olaciregui, Melanie Valenti, Ruth Ruddle, Alan Henley, Angela Hayes, Alexis De Haven Brandon, Alan MacKay, Valeria Molinari, Maria Vinci, Sergey Popov, Paul Brennan, Andrew Moore, Liam Hudson, Swen Hoelder, Alex Bullock, Florence Raynaud, Sue Eccles, Angela Montero Carcaboso, Chris Jones
Journal: Neuro-Oncology (2016)

We recently reported somatic mutations in ACVR1, encoding the serine/threonine kinase ALK2 receptor, in diffuse intrinsic pontine glioma (DIPG) and have explored its utility as a novel drug target in these incurable childhood brainstem tumours. 50/206 (24%) DIPG patients harboured ACVR1 mutations, with the extended survival times (p=0.0028) and HIST1H3B K27M associations (p=0.046) of this genotype restricted to G328E/V/W substitutions; the common germline variant in fibrodysplasia ossificans progressiva (FOP), R206H, instead frequently co-segregated with H3F3A K27M and a shorter overall survival. This mutation is reported to confer abnormal responsiveness to activin A in FOP, a phenomenon recapitulated in vitro in both R206H and G328V primary patient-derived DIPG models assessed by Western blot for p-Smad1/5/8 and ID1. Unlike classical BMP ligands, the spatiotemporal expression of activin A in neurodevelopment correlates with the suggested origins of DIPG. Screening mutant and wild-type (wt) DIPG cultures with a range of quinazolinone- and pyrazolo [1,5-a] pyrimidine-based ALK2 inhibitors, both published and newly-derived in-house, demonstrated differential effects on cell viability down to sub-micromolar concentrations, recapitulating genetic knockdown with shRNA, and corresponding to sustained time- and concentration-dependent reduction in signaling. Preclinical studies showed LDN-193189 and LDN-214117 to be orally bioavailable and tolerated, with penetration in the CNS at potentially efficacious doses. Treatment of mice bearing orthotopic xenografts of H3F3A K27M, ACVR1 R206H mutant HSJD-DIPG-007 cells with 25mg/kg of LDN-193189 for 28 days significantly reduced tumour burden and extended survival compared to vehicle control (p=0.0023), an effect not observed in an H3F3A/ACVR1 wild-type orthotopic model. Continued development of novel ALK2 inhibitors with increased potency, selectivity and pharmacokinetic properties may play an important role in future trials of DIPG patients.
OS6.2 Medulloblastoma recurrence: Improved survival with a metronomic and targeted antiangiogenesis therapy - experience in 18 patients
Authors: I. Slavc, A. Peyrl, A. A. Azizi, J. Gojo, M. Chocholous, T. Czech, K. Dieckmann, C. Haberler
Journal: Neuro-Oncology (2016)
Only Dendritic Cells, but Not Lymphocytes, Acquired Tolerogenicity by PUVA-Treatment by Upregulation of Indoleamine 2,3-Dioxygenase (IDO)
Authors: Hideaki Maeba, Rie Kuroda, Yo Niida, Shintaro Mase, Raita Araki, Toshihiro Fujiki, Akihiro Yachie, Shoichi Koizumi, Ryosei Nishimura
Journal: Blood (2011)
Interim safety and efficacy of a randomized (1:1), open-label phase 2 study of talimogene laherparepvec (T) and ipilimumab (I) vs I alone in unresected, stage IIIB-IV melanoma
Authors: J. Chesney, F. Collichio, R.H.I. Andtbacka, I. Puzanov, J. Glaspy, M. Milhem, O. Hamid, L. Cranmer, Y. Saenger, M. Ross, L. Chen, J.J. Kim, H.L. Kaufman
Journal: Annals of Oncology (2016)
Efficacy and safety of first-line gefitinib treatment in metastatic lung adenocarcinoma patients with sensitizing EGFR mutation determined by ddPCR in plasma cell-free DNA (BENEFIT trial)
Authors: J. Wang, Y. Cheng, Y.-L. Wu, T. An, H. Gao, K. Wang, Q. Zhou, Y. Hu, Y. Song, C. Ding, X. Ye, F. Peng, L. Liang, Y. Hu, C. Huang, C. Zhou, Y.-K. Shi, L. Zhang, Y. Gu
Journal: Annals of Oncology (2016)
Capecitabine and streptozocin ± cisplatin for gastroenteropancreatic neuroendocrine tumours: predictors of long-term survival in the NET01 trial
Authors: T. Meyer, W. Qian, J.W. Valle, D. Talbot, D. Cunningham, N. Reed, L. Wall, J. Waters, P. Ross, A. Anthoney, K. Sumpter, N. Sarwar, T. Crosby, N. Begum, G. Young, R. Hardy, P. Corrie
Journal: Annals of Oncology (2016)
Pembrolizumab (pembro) as first-line therapy for advanced/unresectable or metastatic urothelial cancer: Preliminary results from the phase 2 KEYNOTE-052 study
Authors: A. Balar, J. Bellmunt, P.H. O'Donnell, D. Castellano, P. Grivas, J. Vuky, T. Powles, E.R. Plimack, N.M. Hahn, R. de Wit, L. Pang, M.J. Savage, R. Perini, S. Keefe, D. Bajorin
Journal: Annals of Oncology (2016)
Postapproval Observational Studies of Non–Vitamin K Antagonist Oral Anticoagulants in Atrial Fibrillation
Authors: Tatjana S. Potpara, Gregory Y. H. Lip
Journal: JAMA (2017)

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Evaluation of the conversion rate in Ki-67, estrogen receptor (ER), progesterone receptor (PR) and HER2 between primary breast cancer and relapse and their value as a prognostic factor
Authors: I. Blancas López-Barajas, A. Muñoz, M. Legerén, F. Galvez, R. González, J.M. Jurado, C.J. Rodriguez, M. Delgado, B. Gonzalez Astorga, M. Yélamos, S. Sequero, V. Chacon
Journal: Annals of Oncology (2016)
Efficacy of second and third generation EGFR tyrosine kinase inhibitors, alone or in combination, in T790M-mediated resistance
Authors: F. Papaccio, C.M. Della Corte, G. Viscardi, G. Esposito, M. Fasano, F. De Vita, M. Orditura, F. Ciardiello, F. Morgillo
Journal: Annals of Oncology (2016)
The Clinical Outcome of Newly Diagnosed Patients &gt;60 Years of Age with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Standard or Liposomal Chemotherapies
Authors: Mohamed Amin Ahmed, Yasuhiro Oki, Mansoor Noorani, Loretta Nastoupil, Luis E. Fayad, Fredrick B. Hagemeister, Alma Rodriguez, Richard Eric Davis, Jason R Westin
Journal: Blood (2015)
IMST-45. A FULLY-HUMAN EGFRvIII-TARGETED BISPECIFIC ANTIBODY REDIRECTS HUMAN T CELLS TO SPECIFICALLY LYSE MALIGNANT GLIOMA
Authors: Patrick C. Gedeon, Teilo H. Schaller, Carter M. Suryadevara, Bryan D. Choi, Elizabeth A. Reap, Gary E. Archer, Luis Sanchez-Perez, Darell D. Bigner, John H. Sampson
Journal: Neuro-Oncology (2016)
CSIG-06. BRACHYURY AND ITS UPSTREAM, PI3K/AKT PATHWAY, ARE INVOLVED IN GROWTH OF SKULL BASE CHORDOMA
Authors: Ryohei Otani, Akitake Mukasa, Masahiro Shin, Mayu Omata, Shunsaku Takayanagi, Shota Tanaka, Keisuke Ueki, Nobuhito Saito
Journal: Neuro-Oncology (2016)

Chordoma is a slow glowing tumor that rarely metastasizes, but is a clinically malignant tumor. Surgical extirpation is not feasible in most cases, and no adjuvant therapy currently available can sufficiently control the local recurrence, resulting in ominous outcome in many cases. To improve the outcome, a strategy to target an appropriate molecule may be needed. As a candidate for such target, we investigated Brachyury, a transcription factor involved in notochord development. Brachyury expression was evaluated by quantitative RT-PCR (qRT-PCR) in 27 chordoma samples, and it was overexpressed in all of the 27 chordoma studied. Patients with higher Brachyury expression (n=11) had shorter PFS (5 month) than those with lower expression (n=16, 13 month). Copy number of Brachyury gene was estimated by quantitative PCR, and 12 of 27 (44%) showed copy number gain in the tumor (average ± SD = 2.6 ± 0.6). There was a positive correlation between Brachyury expression and its copy number (R=0.61, p=0.0002). Comparison of gene expression pattern in Brachyury-high tumors (n=4) vs. Brachyury-low tumors (n=4) by expression microarray demonstrated up-regulation of PI3K/Akt pathway genes, and suppression of PI3K led to decrease of Brachyury expression in chordoma cell line U-CH2. Our study indicated PI3K/Akt pathway activation and Brachyury overexpression appear to be key events in chordoma growth regulation, and suggests targeting those pathways may be a good candidate for a new approach aiming at growth suppression and better control of chordomas.
STMC-10. STEM CELL-BASED SUICIDE GENE THERAPY FOR MALIGNANT GLIOMA UTILIZING MUSE CELLS TRANSDUCED WITH HSVtk GENE
Authors: Makoto Horikawa, Tomohiro Yamasaki
Journal: Neuro-Oncology (2016)

Treatment of malignant gliomas is extremely difficult because of their invasive nature. Surgical resection is almost always followed by regrowth of residual tumor cells in adjacent normal brain. To improve the prognosis of malignant glioma, we have attempted to explore stem cell-based suicide gene therapy (HSVtk/GCV system) using Multilineage-differentiating stress-enduring (Muse) cells as a vehicle because of their inherent tumor-tropic properties. In the present study, we demonstrated potent in vitro and in vivo bystander effects of Muse cells transduced with HSVtk gene (Muse-tk cells). Proliferation activity of U87 and U251 human glioma cells in the medium containing 2 µg/ml of GCV was inhibited only when the tumor cells were co-cultured with Muse-tk cells. The inhibition was significant at the Muse-tk:tumor cell ratio of as low as 1:64. The proliferation of U87 and U251 glioma cells was not inhibited in the medium containing 2 µg/ml of GCV, when Muse-tk cells were not present. Real-time bystander effect between Muse-tk and U87 cells observed under a culture microscope. Co-implantation experiment with a mixture of U87 human glioma and Muse-tk cells at various ratios in the nude mouse brain demonstrated only 1/16 Muse-tk cells to the tumor cells were needed for complete tumor eradication. Next, a pre-existing intracranial U87 glioma was treated with intratumoral injection of Muse-tk cells followed by GCV administration. Tumor size significantly decreased and survival time significantly prolonged in the therapeutic group compared with the control group. Finally, we confirmed that the implanted Muse-tk cells in the brain were eliminated after GCV administration by using real time PCR. These results indicate feasibility and safety of this therapy. We are planning to progress to human clinical trials of allogeneic Muse cell-mediated suicide gene therapy in patients with malignant glioma.
Enhanced Elimination of 6-Mercaptopurine or Methotrexate-Treated Acute Lymphoblastic Leukemia Cells by Natural Killer Lymphocytes In Vitro: A Potential Mechanism of Action of Maintenance Chemotherapy
Authors: Abdual H. Siddiqui, Mohammad Bhuiyan, Akila Muthukumar, Steven Buck, Yaddanapudi Ravindranath, Sureyya Savasan
Journal: Blood (2010)
Pembrolizumab in combination with pomalidomide and low-dose dexamethasone in refractory or relapsed and refractory multiple myeloma (rrMM): Randomized, phase 3 KEYNOTE-183 study
Authors: E.M. Ocio, J. Shah, S. Jagannath, M.-V. Mateos, A. Palumbo, U. Kher, P. Marinello, J. San Miguel
Journal: Annals of Oncology (2016)
Autoimmune Hemolytic Anemia (AIHA) in Children: A French Observational Study of 171 Patients for the French Society of Pediatric Hematology and Immunology (SHIP).
Authors: Nathalie Aladjidi, Antoine Pariente, Thierry Leblanc, Brigitte Bader Meunier, Yves Bertrand, Gerard Michel, Francoise Ledeist, Yves Colin, Genevieve Chene, Brigitte Nelken, Guy Leverger, Yves Perel
Journal: Blood (2005)
Adverse Effect of Very Poor Cytogenetics and Monosomal Karyotype On Outcomes Following T-Deplete Reduced Intensity Conditioned Stem Cell Transplant for MDS and AML.
Authors: Pramila Krishnamurthy, Victoria T Potter, Austin G Kulasekararaj, Victor Noriega, Hugues de Lavallade, Robin M. Ireland, Stephen Devereux, Judith C. W. Marsh, Robert E. Marcus, Barbara Czepulkowski, Antonio Pagliuca, Ghulam J. Mufti
Journal: Blood (2012)
Preclinical Characterization of the JAK-2 Inhibitor, SGI-1252
Authors: Kausar Begam Riaz Ahmed, Roberto H Nussenzveig, Andrew T. Chen, Josef T. Prchal, Charles J. Parker, Eric Gourley, Paul Severson, Jared Bearss, Carissa Jones, Steven L. Warner, David Vollmer, David J. Bearss
Journal: Blood (2008)
IKZF1 (IKAROS) Deletions Are Independent On BCR-ABL1 Rearrangement and Are Associated with a Peculiar Gene Expression Signature and Poor Prognosis in Adult B-Progenitor Acute Lymphoblastic Leukemia (ALL) Patients.
Authors: Ilaria Iacobucci, Monica Messina, Nunzio Iraci, Annalisa Lonetti, Sabina Chiaretti, Anna Ferrari, Cristina Papayannidis, Francesca Messa, Antonella Vitale, Francesca Paoloni, Daniela Cilloni, Clelia Tiziana Storlazzi, Emanuela Ottaviani, Stefania Paolini, Sandra Durante, Simona Soverini, Rita Guarini, Marco Vignetti, Fabrizio Pane, Giuseppe Saglio, Robin Foà, Markus Muschen, Heike Pfifer, Oliver Ottmann, Giovanni Perini, Michele Baccarani, Giovanni Martinelli
Journal: Blood (2009)