tbuckley/cabot-search huggingface dataset:
Reversal of Drug/TRAIL-Resistant B-NHL Cells to Apoptosis by the Combination of Rituximab (anti-CD20) and Either Mapatumumab or Lexatumumab
Authors: Mario I. Vega, Sara Huerta-Yepez, Melisa Martinez-Paniagua, Stavroula Baritaki, Haiming Chen, James R. Berenson, Benjamin Bonavida
Journal: Blood (2010)
High Efficacy and Particular Safety Profile of Imatinib Mesylate (Glivec®) in Elderly Patients with CML in Chronic Phase: Results of the AFR04 Prospective Study.
Authors: Philippe Rousselot, Franck Nicolini, François Xavier Mahon, Delphine Réa, Jérome Jaubert, Christian Berthou, Josy Reiffers, Joelle Guilhot, François Guilhot
Journal: Blood (2007)
Efficacy and pharmacogenomic correlation of the combination of oxaliplatin and paclitaxel in first line advanced non-small cell lung cancer (NSCLC). Preliminary results of the Spanish Lung Cancer Group (SLCG) 0103 phase II trial
Authors: P. Garrido Lopez, D. Isla, B. Gil, M. López-Brea, P. Lianes, J. González Larriba, B. Medina, M. Sánchez Ronco, M. Taron, R. Rosell
Journal: Journal of Clinical Oncology (2006)

7122 Background: Ox is an attractive platinum analogue that has not been fully explored in NSCLC. We tested the combination of ox/pac as first-line therapy in NSCLC. We also assessed single nucleotide polymorphisms (SNPs) in several DNA repair genes (XRCC1 Arg399Gln, XRCC3 Met241Thr, XPD Lys751Gln and XPD Asp312Asn) and correlated the results with outcome in these patients (p). Methods: 68 stage IIIB (pleural effusion) and IV NSCLC p received up to 6 cycles of p 200 mg/m 2 on day 1 plus ox 130 mg/m 2 on day 2 every 21 days. Response was assessed after the third and sixth cycles. SNPs were determined by TaqMan assay in peripheral blood extracted at baseline Results: p characteristics: median age 62; 82% male; performance status 0, 54.5%; adenocarcinoma 48%; CNS metastases (mets), 15%, liver mets, 17%. 259 cycles delivered. Grade (G) 3–4 toxicity profile: neutropenia 11%; febrile neutropenia 8%; neurosensory (G3) 5%; asthenia (G3) 8%; diarrhea (G3) 5%. Laryngodysesthesia was observed in 1 p. There were 2 deaths due to neutropenic fever. In 52 evaluable p, overall response rate was 48% (PR 46%, CR 2%, SD 6%, PD 21%). Median time to progression was 4.4 months (m) (95% CI, 2.9–5.9 m). Median survival was 7.9 m (95% CI, 5.5–10.3 m). Conclusions: The combination of ox/pac offers similar results to other platinum-based regimens with an acceptable different toxicity profile and without a significant increase in neurotoxicity. Final data on response, time to progression and survival according to SNPs will be presented. No significant financial relationships to disclose.
Liposomal prednisolone inhibits tumor growth in a spontaneous mouse mammary carcinoma model
Authors: Anil K. Deshantri, Sander A.A. Kooijmans, Sylvia A. Kuijpers, Maria Coimbra, Astrid Hoeppener, Gert Storm, Marcel H.A.M. Fens, Raymond M. Schiffelers
Journal: Journal of Controlled Release (2016)
In Multiple Myeloma, Clonal Cells Are Unevenly Distributed among Peripheral Blood B Cell Subpopulations.
Authors: Stefanos I. Papadhimitriou, Ioanna Gligori, Elpiniki Kritikou-Griva, Georgios Gortzolidis, Aggeliki Davea, Georgios S. Paterakis, Eleni Goumakou, Ioanna Savvidou, Vassiliki Grigoraki, Nikolaos I. Anagnostopoulos, Maria Georgiakaki
Journal: Blood (2004)
Abstract B27: Blockade of protein kinase A (PKA) localization augments the trafficking and anti-tumor efficacy of adoptively transferred chimeric antigen receptor-expressing T cells
Authors: Kheng Newick, Shaun O'Brien, Jing Sun, Veena Kapoor, Steve Maceyko, Albert Lo, Ellen Pure, Ed K. Moon, Steven M. Albelda
Journal: Cancer Research (2016)

Abstract Infusion of T cells expressing chimeric antigen receptors (CAR T cells) is still relatively ineffective in solid tumors due to the presence of immunosuppressive mediators (such as prostaglandin E2 (PGE2) and adenosine), and poor T cell trafficking. Since PGE2 and adenosine activate protein kinase A (PKA), which then inhibits T cell receptor (TCR) activation, we generated CAR T cells that expressed a small peptide called the “regulatory subunit I anchoring disruptor” (RIAD) that inhibits the association of protein kinase A (PKA) with ezrin; this interaction is required for the negative effects of PKA on TCR activation. After exposure to PGE2 or adenosine in vitro, CAR-RIAD T cells showed increased TCR signaling, more cytokine release, and enhanced killing of tumor cells compared to CAR T cells. When injected into tumor-bearing mice, murine and human CAR-RIAD T cells demonstrated enhanced anti-tumor efficacy compared to CAR T cells due to increased T cell infiltration of established tumors, and attenuated tumor-induced hypofunction. Subsequent in vitro assays showed that both mouse and human CAR-RIAD cells migrated more efficiently than CAR cells in response to the chemokine CXCL10 and also adhered better to various matrices. Our data therefore show that the addition of the RIAD peptide to adoptively transferred CAR T cells augments their efficacy by increasing their effector function and by improving trafficking into tumor sites. This treatment strategy should therefore be considered for clinical application in treating solid tumors. Citation Format: Kheng Newick, Shaun O'Brien, Jing Sun, Veena Kapoor, Steve Maceyko, Albert Lo, Ellen Pure, Ed K. Moon, Steven M. Albelda. Blockade of protein kinase A (PKA) localization augments the trafficking and anti-tumor efficacy of adoptively transferred chimeric antigen receptor-expressing T cells. [abstract]. In: Proceedings of the AACR Special Conference: Function of Tumor Microenvironment in Cancer Progression; 2016 Jan 7–10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2016;76(15 Suppl):Abstract nr B27.
Whole-Exome Sequencing to Identify Mutations in Thrombosis Modifier Genes Isolated From a Factor V Leiden-Dependent Sensitized ENU Suppressor Screen in the Mouse
Authors: Randal Joseph Westrick, Guojing Zhu, Jishu Xu, Audrey C.A. Cleuren, Angela Yang, David R Siemieniak, Kart Tomberg, Weiping Peng, Jun Z Li, David Ginsburg
Journal: Blood (2011)
Validation for a novel diagnostic standard in HPV-positive oropharyngeal squamous cell carcinoma.
Authors: Xiao-Jun Ma, Andrew Schache, Triantafilos Liloglou, Janet Risk, Terence Jones, Hongwei Wang, Son Bui, Yuling Luo, Philip Sloan, Richard Shaw, Max Robinson
Journal: Journal of Clinical Oncology (2012)

5543 Background: HPV testing is now widely advocated in the work up of oropharyngeal squamous cell carcinoma (OPSCC). The "gold standard" for oncogenic HPV detection is the demonstration of transcriptionally active high-risk HPV in fresh tumour tissue. For clinical utility, testing strategies have necessarily focused on formalin-fixed paraffin-embedded (FFPE) tissue, but this has been at the expense of reduced sensitivity and specificity for oncogenic HPV. This study evaluates a novel RNA-based in situ hybridisation test against the analytical gold standard; detection of high-risk HPV mRNA, derived from fresh frozen tissue samples, by quantitative reverse transcriptase polymerase chain reaction (qPCR). Methods: A tissue-microarray comprising FFPE cores from 79 OPSCC was tested using High Risk HPV RNAscope (Advanced Cell Diagnostics, USA) for HPV16, 18, 31, 33, 35, 52, and 58. Analytical accuracy and capacity for prognostic discrimination was determined by comparison with HPV RNA qPCR for HPV16, 18 and 33. Demographic and tumour parameters were compared by Chi-squared and Kruskal-Wallis tests. Test sensitivity and specificity were calculated against the standard. Kaplan–Meier survival estimates were constructed to assess prognostication. Results: High risk HPV RNAscope had sensitivity and specificity of 97% and 93% respectively (PPV 91%, NPV 98%) by comparison to the gold standard. Kaplan-Meier estimates of disease specific survival (DSS, p=0.002) and overall survival (OS, p&lt;0.001) by RNAscope were similar to the gold standard (DSS, p=0.006, OS, p=0.002) and superior to p16 immunohistochemistry (IHC) or the combination of p16 IHC and DNA qPCR. Conclusions: We demonstrated that High Risk HPV RNAscope can be used to detect oncogenic HPV in FFPE OPSCC samples and has both excellent analytical and prognostic performance against the gold standard test for oncogenic HPV. These results raise the possibility that High Risk HPV RNAscope could be adopted as an ‘international standard’ test for OPSCC in clinical practice. As the oncology community approaches therapeutic de-escalation based on HPV status, such a reliable and efficacious test may have immediate application.
P0555 : Insertions and/or deletions in the main regulatory region of hepatitis B virus suggest multicoding of the X protein
Authors: A. Caballero, J. Gregori, M. Buti, D. Tabernero, J. Quer, M. Blasi, F. Rodriguez-Algarra, R. Casillas, C. González, I. Belmonte, L. Nieto, X. Costa, R. Esteban, M. Homs, F. Rodriguez-Frías
Journal: Journal of Hepatology (2015)
Phenomenon of Pain In Thalassemia: A Prospective Analysis by the Thalassemia Clinical Research Network (TCRN)
Authors: Dru Haines, Susan Carson, Sage Green, Marie Martin, Thomas D. Coates, Olivia Oliveros Vega, Eric Gerstenberger, Jennifer Braunstein, Diane Calamaras, Renata Dzackova, Patricia Giardina, Dorothy Klienert, Janet Kwiatkowski, Tito R. Mendoza, Manuela Merelles-Pulcini, Ellis J. Neufeld, Nancy F. Olivieri, Leann Schilling, Elliott Vichinsky, Felicia Trachtenberg
Journal: Blood (2010)
EGFR mutations and gefitinib sensitivity in patients with metastatic non-squamous non-small cell lung cancer
Authors: V. Moiseyenko, E. Imyanitov, E. Levchenko, S. Procenko, R. Orlova, A. Iyevleva, K. Buslov, Y. Ulibina, D. Matsko, F. Moiseyenko
Journal: Journal of Clinical Oncology (2008)

19075 Background: Probability of clinical benefit from EGFR tyrosine kinase inhibitors in previously treated NSCLC pts is strongly associated with the presence of EGFR mutation. However, the experience of gefitinib application as the first-line therapy in mutation-positive pts remains limited. Methods: EGFR analysis included the detection of the exon 19 deletions and 858TG mutation in paraffin embedded tumor specimens. Chemo-naïve mutation-positive pts received gefitinib (250 mg/d p.o.) until disease progression or unacceptable toxicity. The primary outcome was the response rate (RR) according to RECIST criteria. Results: tumor specimens from 52 pts with advanced non-squamous NSCLC were enrolled (median age - 58,6 years; adenocarcinomas - 82%, BAC - 8%, other - 10%). EGFR mutations were found in 11 of 52 pts (21%) with adenocarcinomas only. 9 mutations were exon 19 deletions and 2 - codon 858 substitutions. 6 chemo-naïve pts with stage IV adenocarcinomas were selected for treatment with gefitinib (median age: 62,6 years; M/F - 4/2; ECOG PS 1/2/3 - 2/3/1; exon 19 deletions - 6/6). Adverse events were mainly grade 1–2 rash (4/6) and grade 3 rash in 2 pts. The overall RR was 67% (PR 67% and CR 0%) (4/6) with disease stabilization in 33% (2/6). Median time to disease progression was 8.0 months (2.5–12.5 months). Conclusions: 1st-line gefitinib therapy in EGFR mutation-positive NSCLC pts is feasible, well tolerated, and yields a substantial RR and PFS. No significant financial relationships to disclose.
Sunitinib malate is active and synergistic with cisplatin against human urothelial carcinoma in a preclinical model
Authors: G. Sonpavde, W. Jian, S. P. Lerner
Journal: Journal of Clinical Oncology (2007)

15632 Background: Sunitinib malate is an oral, multitargeted tyrosine kinase inhibitor of VEGFRs, PDGFRs, KIT, RET, and FLT3, approved multinationally for the treatment of advanced RCC and imatinib-resistant or -intolerant GIST. Angiogenesis and plasma VEGF correlate with poor outcomes in human urothelial carcinoma. We designed a preclinical study to examine the efficacy of sunitinib malate alone and in combination with cisplatin against human urothelial carcinoma in vitro and in a murine xenograft model. Methods: The IC 50 for sunitinib malate and cisplatin was determined separately against two human urothelial carcinoma cell lines (TCC-SUP and 5637). Sunitinib malate and cisplatin were also applied concurrently to determine activity of the combination. Immunohistochemical staining was performed to detect expression of VEGFR2 on the cell lines, and to measure modulation of this pathway by sunitinib by measuring phosphorylated (p)VEGFR2. Anti-tumor activity of sunitinib malate alone and in combination with cisplatin was determined in a murine xenograft model bearing 5,637 cells. Results: Both human urothelial carcinoma cell lines were found to express VEGFR2. Sunitinib malate displayed significant activity against both urothelial carcinoma cell lines in vitro at low nanomolar concentrations. Furthermore, sunitinib malate in combination with cisplatin was synergistic in vitro. We observed primarily cytostatic activity for sunitinib malate at both 20 mg/kg and 40 mg/kg orally once daily against a murine xenograft model bearing subcutaneous 5,637 cell tumors during 4 weeks of treatment. Anti-tumor activity of sunitinib malate in combination with cisplatin and correlative studies are being evaluated in the murine xenograft model. Conclusion: Sunitinib malate has anti-tumor activity against human urothelial carcinoma as a single agent and is synergistic in combination with cisplatin in vitro. Sunitinib also has significant efficacy in a murine xenograft model of human urothelial carcinoma. These results warrant further exploration of sunitinib malate as a single agent and in combination with cisplatin chemotherapy in human urothelial carcinoma. No significant financial relationships to disclose.
Frederick John Pickworth
Authors: Tony Pickworth
Journal: BMJ (2016)

Frederick John Pickworth was a general practitioner, who for a large part of his career lived, and worked singlehandedly in the village of Barnt Green, Worcestershire. He was a shining example of what might be considered “the golden age” of primary care.

He was born in Birmingham, the son of two doctors, and attended King Edward’s School. At the age of 16 he was involved in a motorcycle accident while riding a school motorbike, which resulted in amputation of his right leg above the knee. Yet he returned to full time education at school after six weeks, and within two years he had started at medical school in Birmingham.

In fact …
18F-Choline Uptake in Acute Ischemic Stroke
Authors: Kostas Delaunay, Florence Le Jeune, Etienne Garin, Anne Devillers, Xavier Palard-Novello
Journal: Clinical Nuclear Medicine (2016)

A 75-year-old man with a history of prostate cancer was referred to our department to perform F-choline (FCH) PET/CT. FCH PET/CT showed a markedly increased uptake in the right temporoparietal junction brain. Three weeks earlier, acute ischemic stroke was diagnosed in the right temporoparietal junction brain on diffusion-weighted sequence and thrombosis in a distal branch of the right middle cerebral artery on MR angiography. Choline precursors promote repair and growth of cell membranes in neurologic diseases, so FCH PET/CT uptake could be explained by repair processes during early outcome of acute ischemic stroke.
A cost-effectiveness analysis evaluating allogeneic hematopoietic cell transplantation (AHCT) versus consolidation chemotherapy for the treatment of acute myeloid leukemia (AML) in first complete remission.
Authors: Abby Statler, Mendel Singer, Anjali S. Advani
Journal: Journal of Clinical Oncology (2014)

6556 Background: The objective of this study was to determine which treatment strategy for AML in first complete remission (CR) is more cost-effective: consolidation chemo or AHCT. Methods: Simple decision analyses were performed for the cost and the effectiveness of each strategy; the cost-effectiveness was subsequently compared using incremental cost-effectiveness analysis. The population modeled included AML pts < 60 years old in first CR. The majority of the outcome data pulled from the literature included pts with unfavorable cytogenetics (poor/intermediate risk AML). The analyses assumed a 5-year time horizon and assessed medical costs and health benefits, which were measured in quality adjusted life years (QALYs). Costs and QALYs were discounted 3% per year. Sensitivity analyses were performed on the probabilities, costs, and utilities. Results: Chemo was the more effective (2.67 vs. 1.79 QALYs; 3.04 vs. 2.15 5 year overall survival) and less expensive ($163,391 vs. $182,018) strategy. Chemo was cost-saving compared to AHCT, i.e. it was both more effective and less expensive. The Sensitivity analyses did not change the results. Exploratory sensitivity analyses did however demonstrate if the probability of dying from AHCT was the same as chemo and the probability of relapsing after AHCT was ≤ .17, AHCT would dominate the chemo strategy. Conclusions: The chemo strategy was more effective because its QALY and OS outcomes were superior to AHCT. The contribution of the Quality-of Life (QoL) outcomes depreciated the effectiveness (i.e. QALYs) of each strategy almost equally (chemo: 0.37 vs. AHCT: 0.36). This finding demonstrates although the overall QALYs were greater in the chemo strategy, the contribution of the QoL outcomes were virtually the same for both strategies. As the clinical effectiveness of AHCT improves over time, the QoL outcomes will become more influential. In the future, if the improvement in AHCT efficacy is coupled with a meaningful increase in the AHCT QoL outcomes, AHCT could become the more cost-effective treatment strategy.
ASXL1 Mutations Predict for Resistance to Chemotherapy and Inferior Outcome in Younger Adult Patients with Acute Myeloid Leukemia (AML): A Study of the German-Austrian AMLSG
Authors: Peter Paschka, Richard F. Schlenk, Julia Herzig, Teresa Aulitzky, Verena I. Gaidzik, Lars Bullinger, Marianne Habdank, Andrea Corbacioglu, Daniela Späth, Claus-Henning Köhne, Andrea Kündgen, Marie von Lilienfeld-Toal, Gerhard Held, Heinz A. Horst, Katharina Götze, Martin Bentz, Jürgen Krauter, Arnold Ganser, Hartmut Döhner, Konstanze Döhner
Journal: Blood (2011)
Cap on locum costs saved £600m, says NHS Improvement
Authors: Abi Rimmer
Journal: BMJ (2016)

The NHS in England has saved over £600m (€670m; $730m) since caps on agency staff costs were introduced, says NHS Improvement.

In November 2015 a cap on the hourly rates paid for agency staff were introduced, after claims that the NHS had spent over £3bn on agency staff in 2014-15. Figures obtained by BMJ Careers earlier this year showed that in 2015 NHS acute care trusts in England spent nearly 25 times as much on locum agency fees as they …
Identification of Oncogenic EZH2 Mutations In Myelodysplastic Syndromes and Related Myeloid Malignancies
Authors: Hideki Makishima, Ania Jankowska, Ramon V. Tiu, Hadrian Szpurka, Yuka Sugimoto, Quteba Ebrahem, Zhenbo Hu, Reda Mahfouz, Yogen Saunthararajah, Kathryn Guinta, Mehdi Keddache, Christine L. O'Keefe, Mikkael A. Sekeres, Alan F. List, Michael A McDevitt, Jaroslaw P Maciejewski
Journal: Blood (2010)
Trombophylia Prevalence in 444 Patients with Clinical Suspicion of Thrombosis.
Authors: Joao Carlos C. Guerra, Valdir F. Aranda, Claudio A. Mendes, Nelson Hamerschlak, Nydia S. Bacal, Marjorie P. Colombini, Jacyr Pasternak, Roberta Sitnik, Claudia H. Graca, Joao Renato R. Pinho
Journal: Blood (2006)
Health Related Quality of Life (HRQOL) in Patients Receiving Chemoimmunotherapy with Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) or Fludarabine and Cyclophosphamide (FC) for First Line Therapy with Advanced Chronic Lymphocytic Leukemia (CLL).
Authors: Barbara F. Eichhorst, Kirsten Fischer, Anna- Maria Fink, Guenter Fingerle-Rowson, Anne Westermann, Clemens-Martin Wendtner, Raymonde Busch, Michael Hallek
Journal: Blood (2009)
Circulating Human Platelets Express LRP-1 and uPAR mRNAs and Synthesize the Proteins: The Complex LRP-1, uPAR, PAI-1 and uPA Play a Role in Modulating Fibrinolysis in Platelet-Rich Thrombi
Authors: Olga Panes, Valeria Matus, César González, Claudia G Sáez, Jaime Pereira, Diego Mezzano
Journal: Blood (2012)
Molecular profiling of advanced solid tumors and patient outcomes with genotype-matched clinical trials: the Princess Margaret IMPACT/COMPACT trial
Authors: Tracy L. Stockley, Amit M. Oza, Hal K. Berman, Natasha B. Leighl, Jennifer J. Knox, Frances A. Shepherd, Eric X. Chen, Monika K. Krzyzanowska, Neesha Dhani, Anthony M. Joshua, Ming-Sound Tsao, Stefano Serra, Blaise Clarke, Michael H. Roehrl, Tong Zhang, Mahadeo A. Sukhai, Nadia Califaretti, Mateya Trinkaus, Patricia Shaw, Theodorus van der Kwast, Lisa Wang, Carl Virtanen, Raymond H. Kim, Albiruni R. A. Razak, Aaron R. Hansen, Celeste Yu, Trevor J. Pugh, Suzanne Kamel-Reid, Lillian L. Siu, Philippe L. Bedard
Journal: Genome Medicine (2016)

The clinical utility of molecular profiling of tumor tissue to guide treatment of patients with advanced solid tumors is unknown. Our objectives were to evaluate the frequency of genomic alterations, clinical "actionability" of somatic variants, enrollment in mutation-targeted or other clinical trials, and outcome of molecular profiling for advanced solid tumor patients at the Princess Margaret Cancer Centre (PM). Patients with advanced solid tumors aged ≥18 years, good performance status, and archival tumor tissue available were prospectively consented. DNA from archival formalin-fixed paraffin-embedded tumor tissue was tested using a MALDI-TOF MS hotspot panel or a targeted next generation sequencing (NGS) panel. Somatic variants were classified according to clinical actionability and an annotated report included in the electronic medical record. Oncologists were provided with summary tables of their patients' molecular profiling results and available mutation-specific clinical trials. Enrolment in genotype-matched versus genotype-unmatched clinical trials following release of profiling results and response by RECIST v1.1 criteria were evaluated. From March 2012 to July 2014, 1893 patients were enrolled and 1640 tested. After a median follow-up of 18 months, 245 patients (15 %) who were tested were subsequently treated on 277 therapeutic clinical trials, including 84 patients (5 %) on 89 genotype-matched trials. The overall response rate was higher in patients treated on genotype-matched trials (19 %) compared with genotype-unmatched trials (9 %; p < 0.026). In a multi-variable model, trial matching by genotype (p = 0.021) and female gender (p = 0.034) were the only factors associated with increased likelihood of treatment response. Few advanced solid tumor patients enrolled in a prospective institutional molecular profiling trial were treated subsequently on genotype-matched therapeutic trials. In this non-randomized comparison, genotype-enrichment of early phase clinical trials was associated with an increased objective tumor response rate. NCT01505400 (date of registration 4 January 2012).
Identification of Cooperating Genetic Alterations in RUNX Leukemia Using the Mouse Model for the Human Familial Leukemia, FPD/AML.
Authors: Motomi Osato, Namiko Yamashita, Masatoshi Yanagida, Liqun Huang, Scott Kogan, Masayuki Iwasaki, Takuro Nakamura, Katsuya Shigesada, Norio Asou, Yoshiaki Ito
Journal: Blood (2004)