tbuckley/cabot-search huggingface dataset:
Abstract 4919: Tumor heterogeneity represented in human cancer cell lines
Authors: Lysa-Anne Volpe, John Foulke, Michael Jackson, Luping Chen, David H. Randle, Hannah J. Gitschier, Kelly Gardner, Fang Tian
Journal: Cancer Research (2015)

Abstract EGFR has been found frequently mutated in human cancers, and more than 10% lung cancer patients associated with EGFR mutation. In addition, several critical mutations within the EGFR have been shown as gain of function mutations or can cause drug resistance to the EGFR inhibitors. A panel of ATCC tumor cell lines has been characterized for EGFR mutation and EGFR signaling pathway. Particularly, lung cell line NCI-H1975, which contains both drug sensitive mutation EGFR p.L858R and drug resistant mutation p.T790M, has displayed a resistance to EGFR inhibitor.Overall, NCI-H1975 cell line can be used as a nice model to study drug resistance, as well as to screen novel EGFR inhibitors that overcome the p.T790M-mediated resistance. Moreover, we have used next generation sequencing to analyze the mutation allelic frequency of both mutations, and observed tumor heterogeneity within this cell line. Impact of cell passage numbers on the mutation allele frequency of the cell line was also examined. Furthermore, a novel single cell western blot assay has been used to analyze the EGFR mutation, EGFR protein expression and downstream signaling within individual cells of three lung cancer cell lines at the single cell level. Collectively, NCI-H1975 cell line represents the acquired drug resistance found in clinical cancer patients, and this study demonstrates the tumor heterogeneity represented in human cell lines. Citation Format: Lysa-Anne Volpe, John Foulke, Michael Jackson, Luping Chen, David H. Randle, Hannah J. Gitschier, Kelly Gardner, Fang Tian. Tumor heterogeneity represented in human cancer cell lines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4919. doi:10.1158/1538-7445.AM2015-4919
Fluorescent aminoglycosides reveal intracellular trafficking routes in mechanosensory hair cells
Authors: Dale W. Hailey, Robert Esterberg, Tor H. Linbo, Edwin W. Rubel, David W. Raible
Journal: Journal of Clinical Investigation (2016)

Aminoglycosides (AGs) are broad-spectrum antibiotics that are associated with kidney damage, balance disorders, and permanent hearing loss. This damage occurs primarily by killing of proximal tubule kidney cells and mechanosensory hair cells, though the mechanisms underlying cell death are not clear. Imaging molecules of interest in living cells can elucidate how molecules enter cells, traverse intracellular compartments, and interact with sites of activity. Here, we have imaged fluorescently labeled AGs in live zebrafish mechanosensory hair cells. We determined that AGs enter hair cells via both nonendocytic and endocytic pathways. Both routes deliver AGs from the extracellular space to lysosomes, and structural differences between AGs alter the efficiency of this delivery. AGs with slower delivery to lysosomes were immediately toxic to hair cells, and impeding lysosome delivery increased AG-induced death. Therefore, pro-death cascades induced at early time points of AG exposure do not appear to derive from the lysosome. Our findings help clarify how AGs induce hair cell death and reveal properties that predict toxicity. Establishing signatures for AG toxicity may enable more efficient evaluation of AG treatment paradigms and structural modifications to reduce hair cell damage. Further, this work demonstrates how following fluorescently labeled drugs at high resolution in living cells can reveal important details about how drugs of interest behave.
Allogeneic Stem Cell Transplantation Should Be Performed in First Complete Remission in Adults with Acute Lymphoblastic Leukemia; Strong Antileukemic Activity of Chronic Graft-Versus-Host Disease.
Authors: Seok Lee, Byung-Shik Cho, Sung-Yong Kim, Ki-Seong Eom, Yoo-Jin Kim, Chang-Ki Min, Hee-Je Kim, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min, Jong-Won Park, Chun-Choo Kim
Journal: Blood (2006)
Trifluridine-tipiracil for multidrug-resistant advanced colorectal cancer: A multicenter retrospective study
Authors: Shuji Arita, Tsuyoshi Shirakawa, Yuzo Matsushita, Hozumi Kumagai, Gen Hirano, Akitaka Makiyama, Yoshihiro Shibata, Shingo Tamura, Hitoshi Kusaba, Eishi Baba
Journal: Annals of Oncology (2015)
Modification of Invariant Chain and CLIP Expression Increases the Immunogenicity of Leukemic Blasts to Potentiate Leukemia-Specific T Cell Reactivity
Authors: Marvin M. van Luijn, Martine E.D. Chamuleau, James A. Thompson, Suzanne Ostrand-Rosenberg, Theresia M. Westers, Yuri Souwer, Gert J. Ossenkoppele, S. Marieke van Ham, Arjan A. van de Loosdrecht
Journal: Blood (2008)
Clinical Outcome of Hematopoietic Stem Cell Transplantation (HSCT) Using Plasma Depleted Umbilical Cord Blood Units (UCB) That Were Not Depleted of Red Blood Cells Prior to Cryopreservation.
Authors: Robert Chow, David Gjertson, Joseph Rosenthal, Auayporn Nademanee, Chatchada Karanes, Tang-Her Jaing, Michael Graham, Patrick Tan, Lawrence D. Petz
Journal: Blood (2005)
Sunitinib Treatment Enhances Metastasis of Innately Drug-Resistant Breast Tumors
Authors: Joseph W. Wragg, Victoria L. Heath, Roy Bicknell
Journal: Cancer Research (2016)

Abstract Antiangiogenic therapies have failed to confer survival benefits in patients with metastatic breast cancer (mBC). However, to date, there has not been an inquiry into the roles for acquired versus innate drug resistance in this setting. In this study, we report roles for these distinct phenotypes in determining therapeutic response in a murine model of mBC resistance to the antiangiogenic tyrosine kinase inhibitor sunitinib. Using tumor measurement and vascular patterning approaches, we differentiated tumors displaying innate versus acquired resistance. Bioluminescent imaging of tumor metastases to the liver, lungs, and spleen revealed that sunitinib administration enhances metastasis, but only in tumors displaying innate resistance to therapy. Transcriptomic analysis of tumors displaying acquired versus innate resistance allowed the identification of specific biomarkers, many of which have a role in angiogenesis. In particular, aquaporin-1 upregulation occurred in acquired resistance, mTOR in innate resistance, and pleiotrophin in both settings, suggesting their utility as candidate diagnostics to predict drug response or to design tactics to circumvent resistance. Our results unravel specific features of antiangiogenic resistance, with potential therapeutic implications. Cancer Res; 77(4); 1008–20. ©2016 AACR.
Nominal ISOMERs (Incorrect Spellings Of Medicines Eluding Researchers)—variants in the spellings of drug names in PubMed: a database review
Authors: Robin E Ferner, Jeffrey K Aronson
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To examine how misspellings of drug names could impede searches for published literature. <b>Design</b>&nbsp;Database review. <b>Data source</b>&nbsp;PubMed. <b>Review methods</b>&nbsp;The study included 30 drug names that are commonly misspelt on prescription charts in hospitals in Birmingham, UK (test set), and 30 control names randomly chosen from a hospital formulary (control set). The following definitions were used: <i>standard names</i>—the international non-proprietary names, <i>variant names</i>—deviations in spelling from standard names that are not themselves standard names in English language nomenclature, and <i>hidden reference variants</i>—variant spellings that identified publications in textword (tw) searches of PubMed or other databases, and which were not identified by textword searches for the standard names. Variant names were generated from standard names by applying letter substitutions, omissions, additions, transpositions, duplications, deduplications, and combinations of these. Searches were carried out in PubMed (30 June 2016) for “standard name[tw]” and “variant name[tw] NOT standard name[tw].” <b>Results</b>&nbsp;The 30 standard names of drugs in the test set gave 325 979 hits in total, and 160 hidden reference variants gave 3872 hits (1.17%). The standard names of the control set gave 470 064 hits, and 79 hidden reference variants gave 766 hits (0.16%). Letter substitutions (particularly i to y and vice versa) and omissions together accounted for 2924 (74%) of the variants. Amitriptyline (8530 hits) yielded 18 hidden reference variants (179 (2.1%) hits). Names ending in “in,” “ine,” or “micin” were commonly misspelt. Failing to search for hidden reference variants of “gentamicin,” “amitriptyline,” “mirtazapine,” and “trazodone” would miss at least 19 systematic reviews. A hidden reference variant related to Christmas, “No-el”, was rare; variants of “X-miss” were rarer. <b>Conclusion</b>&nbsp;When performing searches, researchers should include misspellings of drug names among their search terms.
The Myleloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) Derived Total Symptom Score (TSS): An International Trial of 1433 Patients with Myeloproliferative Neoplasms (MPNs),
Authors: Robyn Scherber, Amylou Dueck, Jean-Jacques Kiladjian, Stephanie Slot, Sonja Zweegman, Peter te Boekhorst, Suzan Commandeur, Harry C. Schouten, Federico Sackmann, Ana Kerguelen Fuentes, Dolores Hernandez-Maraver, Heike L. Pahl, Martin Griesshammer, Frank Stegelmann, Konstanze Doehner, Thomas Lehmann, Karin Bonatz, Andreas Reiter, Françoise Boyer, Gabriel Etienne, Jean-Christophe Ianotto, Dana Ranta, Lydia Roy, Jean-Yves Cahn, Claire N. Harrison, Deepti Radia, Pablo J. Muxi, Norman I Maldonado, Carlos Besses, Francisco Cervantes, Peter Johansson, Tiziano Barbui, Giovanni Barosi, Alessandro M. Vannucchi, Francesco Passamonti, Bjorn Andreasson, Maria L Ferarri, Alessandro Rambaldi, Jan Samuelsson, Gunnar Birgegard, Ayalew Tefferi, Ruben A. Mesa
Journal: Blood (2011)
Lenalidomide following rituximab and fludarabine in untreated CLL.
Authors: C. S. Ujjani, S. Jamshed, K. W. Fitzpatrick, E. A. Gehan, J. Crawford, C. M. Broome, P. Cohen, C. Kessler, B. D. Cheson
Journal: Journal of Clinical Oncology (2011)

6558 Background: The combination of fludarabine (F) and rituximab (R) has shown an ORR of 90% (CR 47%) in pts with untreated CLL. Nevertheless, relapse is inevitable. Lenalidomide (L) has shown an ORR of 32-47% (CR 7-9%) in relapsed/refractory CLL. Therefore, we proposed following FR with L monotherapy in pts with untreated CLL in order to improve the CR rate and PFS. Methods: For this 2-stage Phase II study, pts with untreated CLL requiring therapy, a performance status < 2, and adequate organ function were eligible. Pts received R 375 mg/m2 IV on D1 and F 25 mg/m2 IV D1-5 for 3 cycles. Pts with a CR/PR received 3 more cycles of FR followed by 3 cycles of L. Pts with stable (SD) or progressive disease (PD) after 3 cycles of FR were switched to L 5 mg po daily D1-21. If tolerability permitted, L was increased to 10 mg with cycle 2. Pts with at least SD after 3 cycles of L received another 3 cycles. Pts with PD were removed. The primary endpoint was CR rate with FR followed by L monotherapy. Accrual for Stage I has been completed. Results: Of the 21 pts on study, the median age was 61 years, 67% were male, 29% were Rai Stage III/IV, 67% were CD38+, and 33% had a β-2 microglobulin level > 4. Two pts had del 17p, 7 had del 11q, and 5 had sole abnormalities of 13q. Among the 18 pts evaluable for response, the ORR with FR alone was 72.2% (CR 27.8%). With the addition of L in 12 pts, 2 pts converted from a PR to CR, increasing the CR to 38.3% (95% CI 16-60%). One other pt experienced improvement in the bone marrow. L was unable to improve responses in pts refractory to FR. ORRs by cytogenetics were: 50% (del 17p), 50% (del 11q), and 100% (13q abnormality). The median time to response was 7 mos (Range: 6-8 mos). At 13 mo of follow-up, the PFS was 83%. Common grade 3/4 toxicities with FR were neutropenia (66.7%), anemia (16.7%), thrombocytopenia (16.7%), and infection (5.5%). One pt suffered from fatal septic shock during cycle 2. Common grade 3/4 toxicities with L were neutropenia (27.2%), infection (18%), and rash (9%). Pts completed a median of 8 cycles of therapy. The most common reasons for stopping therapy were rash and fatigue. Conclusions: FR followed by L is an efficacious and tolerable regimen for pts with untreated CLL. L monotherapy appears to improve response rate in pts who show a response to FR. Further evaluation is needed.
PTU-018 Emergency readmission following elective endoscopy: audit of 29 868 day-case procedures performed at four teaching hospitals in northwest England
Authors: A Moore, C Ormerod, M McMahon, E Britton, J Ramesh, S Lal, K Bodger, S Sarkar
Journal: Gut (2010)

<h3>Introduction</h3> Despite emergency readmission being a NHS quality indicator and unplanned admission after elective endoscopy a GRS auditable outcome; there is a lack of audit standards and difficulties in attaining these data due to limitations in hospital IT systems. Commercial analytical reporting tools that use NHS administrative data can generate local reports from HES and may serve as a starting point for clinical audit. <h3>Aim</h3> To determine the prevalence, demographics, aetiology and outcomes of emergency readmissions following elective endoscopy. <h3>Methods</h3> From 1.4.08 to 31.3.09 emergency admissions within 6 days of a day-case upper or lower GI endoscopy (ERCP excluded) were identified from analyses of NHS administrative data at RLUH, AUH, SRH, and SMUH. Using a standard proforma, each readmission was audited using case notes, endoscopy database, and the hospital informatics systems. Two senior doctors determined the validity of the admission subdividing them into; unrelated, possible and definite with the latter two categories defining an endoscopy readmission. <h3>Results</h3> Of the 29 868 daycases, 235 admissions were identified, of which 147 were endoscopy readmissions. The following data all relates to endoscopy readmissions. <b>Demographics</b> Male:Female ratio=1:1; Mean age (SD): 65.1 years (17). <b>Readmission rate</b> overall was 0.49% (0.56% for upper and 0.42% for lower GI procedures) with highest rates for therapeutic uppers (1.75%) &gt; therapeutic lowers (0.56%) &gt; diagnostic upper (0.47%) &gt; diagnostic lower (0.38%). <b>Aetiology</b> The most common reasons for admission were vascular events (26.5%) &gt; Symptoms such as pain (17%), GI haemorrhage (17%), suspected/confirmed perforation (17% (confirmed 6.1%))&gt; respiratory (10.2%) causes &gt;bowel obstruction (4.8%): <b>Investigations</b> 71% required simple blood tests and/or x-rays and 26%, cross-sectional imaging. <b>Treatment</b> 84.4% required only observation, 4.8%; surgery, 2.7%; repeat endoscopy, and 7.5% IV antibiotics. <b>Outcomes</b> 24.5% were short-stays discharges from either AED, or medical/Surgical assessment units. Mean LOS was 8.2 (13) days and 30-day mortality was 6.8%. <h3>Conclusion</h3> Commercial analytical reporting tools combined with local interpretation and multicentre collaboration was essential for determining useful information regarding endoscopy readmissions. Readmission rates predictably varied with the procedure type (0.38–1.75%) with therapeutic procedures having the highest. While most patients required simple observation/supportive care, LOS was considerable and mortality rate among readmitted cases was significant.
Tandem Autologous Hematopoietic Progenitor Cell Transplantation (AHPCT) for High-Risk Hodgkin Lymphoma: Mature Results of a Prospective Trial
Authors: Robert M Dean, Matt Kalaycio, Brad Pohlman, Ronald Sobecks, Edward A. Copelan, Brian T. Hill, Lisa Rybicki, Shawnda Tench, Brian J. Bolwell
Journal: Blood (2012)
Androgen deprivation therapy for prostate cancer and the risk of hospitalisation for community-acquired pneumonia
Authors: Blánaid M Hicks, Hui Yin, Franck Bladou, Pierre Ernst, Laurent Azoulay
Journal: Thorax (2016)

<h3>Background</h3> Androgens have been shown to influence both the immune system and lung tissue, raising the hypothesis that androgen deprivation therapy (ADT) for prostate cancer may increase the risk of pneumonia. Thus, the aim of this study was to determine whether ADT is associated with an increased risk of hospitalisation for community-acquired pneumonia in patients with prostate cancer. <h3>Methods</h3> This was a population-based cohort study using the United Kingdom Clinical Practice Research Datalink linked to the Hospital Episode Statistics repository. The cohort consisted of 20 310 men newly diagnosed with non-metastatic prostate cancer between 1 April 1998 and 31 March 2015. Time-dependent Cox proportional hazards models were used to estimate adjusted HRs and 95% CIs for hospitalisation for community-acquired pneumonia associated with current and past use of ADT compared with non-use. <h3>Results</h3> During a mean follow-up of 4.3 years, there were 621 incident hospitalisations for community-acquired pneumonia (incidence rate: 7.2/1000 person-years). Current ADT use was associated with an 81% increased risk of hospitalisation for community-acquired pneumonia (12.1 vs 3.8 per 1000 person-years, respectively; HR 1.81, 95% CI 1.47 to 2.23). The association was observed within the first six months of use (HR 1.73, 95% CI 1.23 to 2.42) and remained elevated with increasing durations of use (≥25 months; HR 1.79, 95% CI 1.39 to 2.30). In contrast, past ADT use was not associated with an increased risk (HR 1.23, 95% CI 0.95 to 1.60). <h3>Conclusions</h3> The use of ADT is associated with an increased risk of hospitalisation for community-acquired pneumonia in men with prostate cancer.
Corrigendum to “The role of hepassocin in the development of non-alcoholic fatty liver disease”
Authors: Hung-Tsung Wu, Feng-Hwa Lu, Horng-Yih Ou, Yu-Chu Su, Hao-Chang Hung, Jin-Shang Wu, Yi-Ching Yang, Chao-Liang Wu, Chih-Jen Chang
Journal: Journal of Hepatology (2016)
Quality of contemporary clinical trials in neuroendocrine tumors.
Authors: T. Walter, M. K. Krzyzanowska
Journal: Journal of Clinical Oncology (2011)

e14617 Background: The heterogeneity of neuroendocrine tumors (NETs) makes the interpretation of clinical trials for this disease group challenging. Our aim was to review the quality of phase II and III trials in NETs to inform design of future studies in this area. Methods: We identified studies by conducting a computerized search of MEDLINE. We considered all phase II or III trials of systemic antineoplastic treatments for NETs that were written in English and published between 2000-2010. Information on trial design, description of the study population, primary and secondary endpoints, statistical considerations and results was abstracted from each article using a standardized form. Results: Six phase III and 34 Phase II trials were identified. The majority were single-arm studies (78%). The make-up of the study population was variable: only 22% of trials included patients with one type of tumor (islet cell carcinoma or carcinoid tumor), 43% of trials included patients with both tumor types and 35% of trials included others endocrine cancers. Disease progression at baseline was often not reported (50%) and was present for all patients in only 20% of trials; status of functioning tumor, tumour differentiation and Ki67 index were reported in 35%, 37% and 12% of trials, respectively. The primary end point (PEP) was clearly defined in 75% and was standard (OR, TTP, PFS by WHO or RECIST criteria) in 50% of trials. An identifiable statistical design and predefined sample size were reported in 62% and 65% of trials, respectively. Toxicities were clearly defined and reported in 65% of trials. Interpretation of study results in concordance with predefined criteria described in the Methods section was poor – in 45% of trials the authors’ interpretation was discordant. Among endpoints, OR, PFS or TTP, OS, Biochemical response (CgA), and clinical response were respectively reported in 97%, 77%, 75%, 37%, and 32% of trials. Conflict of interests and study sponsorship were reported in 42% and 55% of trials. Conclusions: The quality of the design and reporting of phase II/III NETs trials is poor. Future trials should focus on more homogenous patient populations and adhere to rigorous definition, reporting and interpretation of population, and trial parameters as well as results.
Does body mass index impact on clinical outcomes in her-2 positive metastatic breast cancer?
Authors: E. Poletto, A.M. Minisini, A. Ferreira, M. Lambertini, F. Poggio, F. Sottotetti, F. Montemurro, E. Pozzi, V. Rossi, E. Risi, C. Dellepiane, V. Sini, S. Ziliani, G. Minuti, S. Mura, D. Grasso, I. Bertolini, L. Del Mastro, F. Puglisi
Journal: Annals of Oncology (2015)
Efficacy of Dasatinib in Patients with Chronic-Phase Chronic Myelogenous Leukemia with Resistance or Intolerance to Imatinib: 2-Year Follow-Up Data from START-C (CA180-013).
Authors: Richard M. Stone, Hagop M. Kantarjian, Michele Baccarani, Jeffrey H. Lipton, Timothy Hughes, Rana Ezzeddine, Eric Bleickardt, Andreas Hochhaus
Journal: Blood (2007)
Scientific Misconduct Hurts
Authors: Christine Laine
Journal: Annals of Internal Medicine (2017)

Letters6 June 2017Scientific Misconduct HurtsChristine Laine, MD, MPHChristine Laine, MD, MPHSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0148 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Mr. Henderson questions whether Annals did not publish Dansinger and colleagues' manuscript when we had the opportunity to review it in 2015 because of Finelli's review, the editors were “bamboozled by the currently popular opinion [about] high-density lipoprotein cholesterol,” or it was “unfashionable.” Many issues factor into Annals' editorial decision, but those that Mr. Henderson raises did not. The manuscript reported a secondary analysis of a trial that had already been published, and we judged the amount of new information it provided to be limited relative to other papers under consideration. Thus, issues of priority weighed heavily in ...Reference1. Dansinger M. Dear plagiarist: a letter to a peer reviewer who stole and published our manuscript as his own. Ann Intern Med. 2017;166:143. [PMID: 27951597]. doi:10.7326/M16-2551 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M16-2550. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoScientific Misconduct Hurts Christine Laine Scientific Misconduct Hurts George Henderson Metrics Cited byAddressing Reproducibility: Peer Review, Impact Factors, Checklists, Guidelines, and Reproducibility Initiatives 6 June 2017Volume 166, Issue 11Page: 856KeywordsBehaviorDisclosureHigh density lipoprotein cholesterolScientific misconduct ePublished: 6 June 2017 Issue Published: 6 June 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
A Dose Escalation Clinical Trial of Single-Fraction Carbon Ion Radiotherapy for Peripheral Stage I Non–Small Cell Lung Cancer
Authors: Naoyoshi Yamamoto, Tadaaki Miyamoto, Mio Nakajima, Masataka Karube, Kazuhiko Hayashi, Hiroshi Tsuji, Hirohiko Tsujii, Tadashi Kamada, Takehiko Fujisawa
Journal: Journal of Thoracic Oncology (2016)