tbuckley/cabot-search huggingface dataset:
Propensity-score matched pair comparison of accelerated partial breast irradiation (APBI) and whole breast irradiation (WBI) for ductal carcinoma in situ (DCIS).
Authors: John Ben Wilkinson, Ashley Fowler, Ovidiu Marina, Michelle Wallace, Kimberly Marvin, Inga S. Grills, Donald S. Brabbins, Peter Y Chen
Journal: Journal of Clinical Oncology (2013)

1123 Background: DCIS remains a cautionary criterion for APBI by the ASTRO APBI consensus statement. We performed a matched analysis to compare the efficacy of WBI and APBI for patients with DCIS. Methods: Women with DCIS treated with APBI or WBI were reviewed. APBI (n=102) patients with ≥2 y follow-up were matched 1:3 to WBI (n=546) patients with ≥5 y follow-up by age, tumor size, nuclear grade, ER status, margin status, and laterality. Ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), contralateral breast cancer (CLBC) and cause-specific survival (CSS) were compared by cumulative incidence (Gray’s) and competing risks regression (Fine and Gray’s), and overall survival (OS) and disease-free survival (DFS) by Kaplan-Meier (log-rank test). Results: Median follow-up was 4.6 y (2.0-14.7) for APBI and 9.0 y (5.4-27.0) for WBI. Median (range) or percentages are shown (Table). Patients did not differ by match criteria. There were 17 LR, 1 DM, 19 CLBC, 2 CSS, 22 OS, and 19 DFS events during follow-up. The patient groups had similar rates of cancer-related events including ipsilateral and contralateral breast recurrences at both five and eight years. Treatment type, age, tumor size, nuclear grade, ER status, and hormone therapy (HT) were not prognostic of LR or CLBC on uni- and multi-variate analyses. Conclusions: APBI provides equivalent and exemplary outcomes compared to WBI following breast-conserving surgery for DCIS. These findings support previous reports on the efficacy of APBI in the treatment of noninvasive breast carcinoma. Prospective randomized comparison of APBI to WBI for DCIS is needed. [Table: see text]
The Depolymerization of Thymonucleic Acid by an Enzyme System in Normal and Cancerous Hepatic and Mammary Tissues and in the Milk and Sera of Several Species
Authors: Jesse P. Greenstein, Wendell V. Jenrette
Journal: JNCI Journal of the National Cancer Institute (1941)

The Depolymerization of Thymonucleic Acid by an Enzyme System in Normal and Cancerous Hepatic and Mammary Tissues and in the Milk and Sera of Several Species Get access Jesse P. Greenstein, Jesse P. Greenstein research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Wendell V. Jenrette Wendell V. Jenrette junior physiologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 6, June 1941, Pages 845–863, https://doi.org/10.1093/jnci/1.6.845 Published: 01 June 1941
House Keeping Genes in the Human Duodenum are regulated by Changes in Iron Homeostasis
Authors: F Gleeson, E Ryan, S Barrett, J Russell, J Crowe
Journal: Endoscopy (2004)

Aim: A critical parameter in the experimental design of real time RT PCR is the choice of an RNA house keeping gene, helping to interpret the expression profiles of target genes. To identify a suitable house keeping gene for use in gene expression analysis of patients with haemochromatosis and iron deficiency.
A prospective study to compare qPCR to IHC and FISH for the detection of anaplastic lymphoma kinase (ALK) fusions in FFPE specimens from NSCLC patients (<i>PCRTALK</i>).
Authors: David Richard Hout, John Handshoe, Brock Schweitzer, Stephan Wade Morris, Aly Karsan, Helena Daudt, David Saltman
Journal: Journal of Clinical Oncology (2014)

TPS11136 Background: Lung cancer is the most common cause of cancer-related deaths in North America. A number of pharmaceutical firms currently have therapies that target ALK-driven lung cancers in development, with the first-in-class FDA-approved ALK inhibitor Xalkori (crizotinib, Pfizer) demonstrating excellent anti-tumor responses without significant toxicities. There is now substantial interest in ensuring the accurate identification of those NSCLC patients who harbor ALK fusions. The ALK qPCR assay is a quantitative real-time PCR assay that offers high throughput, 24-48 hour TAT, and easily interpretable results. We are performing a clinical diagnostic trial, PCRTALK (PCR tumor ALK), with the primary objective of this trial being to unequivocally demonstrate the performance of the ALK qPCR assayagainst current ALK testing modalities in screening FFPE lung cancer biopsy specimens. The study is recruiting multiple clinical centers throughout Canada for patient enrollment. Once PCRTALK has been completed, our goal is to accomplish the following: (1) the trial will provide clinically relevant data on which types of lung cancer biopsies (bronchoscopy, FNA, CNB, pleural fluid thoracentesis) provide sufficient tissue for the different modalities of ALK testing and report on the number of cases rejected for ALK testing by IHC and FISH due to insufficient tissue; and (2) provide therapeutic outcome data for cases with discordant ALK diagnostic results. A second arm of the study is to conduct a correlative study analyzing both matched FFPE and blood collected from NSCLC patients using various non-invasive methodologies. Methods: The study will proceed according to the following work flow: (1) ALK IHC (ALK IHC-5A4, Leica Biosystems) conducted by BCCA laboratories; (2) 72 individual ALK IHC 5A4-positives and 72 ALK IHC 5A4-negatives selected according to their respective IHC scores and reflexed to 3 - 5; (3) ALK FISH (Abbott Diagnostics) performed on all 144 specimens; (4) The ALK qPCR assay performed on all 144 specimens; and (5) Sanger and/or NGS to determine true status. Initial PCRTALK clinical trial data will be presented together with conclusions based on the results. Clinical trial information: NCT02010047.
Activity and binding mechanism of cetuximab (Erbitux®) to the type III EGF deletion-mutant receptor
Authors: Dipa Patel, Sheetal Patel, Matt Franklin, Xiaoqiang Kang
Journal: Cancer Research (2006)

1238  The epidermal growth factor receptor (EGFR) plays an important role in the growth and survival of many human tumors of epithelial origin. EGFR variant III (EGFRvIII) is a truncated form of EGFR in which residues 6-273 have been deleted; this shortened receptor does not bind ligand, is constitutively active, and is reported to be co-expressed with EGFR on some human tumors including glioblastoma, breast, lung, and prostate. The deleted amino acid residues represent all of domain I and the amino-terminal 2/3 of domain II while domains III and IV of the extracellular region remain intact and should be structurally similar to those of the full-length receptor. Here we have tested the anti-EGFR monoclonal antibody ERBITUX (cetuximab) for its ability to bind EGFRvIII. A crystal structure of the complex of cetuximab bound to wild type EGFR extracellular domain reveals that the antibody binds exclusively to domain III of the receptor. A model of the EGFRvIII protein suggests that cetuximab binding should be unaffected by the deletion and be fully active against this mutant receptor. Chinese hamster ovary (CHO), 32D (non-tumorigenic murine hematopoetic cells), and U87-MG (EGFR positive Glioblastoma cells) stable transfectants were generated that express EGFRvIII. Analysis of receptor phosphorylation showed that EGFRvIII was constitutively phosphorylated in transfected cells. Flow cytometry and immunoprecipitation analysis of EGFRvIII transfectants showed specific binding of cetuximab to EGFRvIII. Binding of cetuximab to EGFRvIII on the cell surface led to the internalization of the cetuximab-EGFRvIII complex. This internalization led to a reduction in phosphorylated EGFRvIII in transfected cells and inhibition of cell proliferation. In addition, cetuximab induced an ADCC reaction in tumor cells expressing EGFRvIII. These results indicate the binding epitope for cetuximab is outside the region of the EGFRvIII deletion, consistent with the model structure. These data suggest that cetuximab may be a potential candidate for the treatment of tumors that also express EGFRvIII.
Serum carbonic anhydrase IX as predictive marker for efficacy of bevacizumab: A biomarker analysis from the GeparQuinto phase III neoadjuvant breast cancer trial.
Authors: Janning Melanie, Volkmar Müller, Eik Vettorazzi, Miguel Cubas-Cordova, Christine Eulenburg, Christian Schem, Peter A. Fasching, Thomas Karn, Tanja N. Fehm, Thorsten Kühn, Friedrich Overkamp, Brigitte Kathrin Rack, Carsten Denkert, Michael Untch, Klaus Pantel, Carsten Bokemeyer, Sibylle Loibl, Gunter Von Minckwitz, Sonja Loges
Journal: Journal of Clinical Oncology (2016)

11505 Background: Appropriate biomarkers to guide selection of patients for treatment with bevacizumab are still urgently needed. In this study, we analyzed serum levels of carbonic anhydrase IX (sCAIX) as potential predictive biomarker in samples from the phase III neoadjuvant GeparQuinto breast cancer trial. Methods: Pre-treatment serum sCAIX levels were determined by Enzyme-linked immunosorbent assay. Correlations between sCAIX levels and pathological complete response (pCR, primary endpoint) and disease-free and overall survival (DFS, OS; secondary endpoints) were assessed with appropriate statistical methods using bootstrapping for robust estimates and internal validation. Results: N = 1189 HER2 negative patients (60% of the study population) of whom 577 received bevacizumab (B) were analyzed. sCAIX levels increased upon addition of 4 cycles bevacizumab to neoadjuvant chemotherapy (NCT) indicating modulation of this biomarker by bevacizumab. When treated with NCT-alone, patients with low sCAIX levels at baseline were less likely to achieve pCR compared to those with higher sCAIX (12.2 % vs. 19.7%, p = 0.02). In patients with low sCAIX levels the addition of bevacizumab to NCT significantly improved the probability to achieve pCR (OR, 2.15; 95%CI, 1.26 to 3.72; p = 0.006 pCR rates: 12.2% for NCT vs. 21.3% for NCT-B), while patients with high sCAIX levels did not benefit from bevacizumab (p = 0.25; test for interaction p = 0.003). DFS was significantly prolonged in patients with higher sCAIX level when they were treated with NCT alone in comparison to NCT-B treated patients (HR, 1.44; 95%CI, 1.05 to 1.99; p = 0.023). For patients with low sCAIX levels DFS was numerically improved with addition of bevacizumab (HR, 0.68; 95%CI, 0.40 to 1.10; p = 0.115, 5-year DFS: 69.5% vs. 80.4%). Conclusions: Depending on sCAIX levels we could identify a patient cohort in primary breast cancer that is potentially undertreated with NCT-alone. Bevacizumab improved pCR rates in this group, suggesting sCAIX as a predictive biomarker for bevacizumab with regards to treatment response. In addition, we showed that bevacizumab is not beneficial in patients with high sCAIX level.
Investigation of Individuals with Positive Endomysial Antibodies and Normal Duodenal Biopsy for Evidence of Coeliac Disease
Authors: B Mohamed, C Feighery, U O'Shea, J Kelly, D Delaney, DS Briain, R Cooney, M Abuzakouk
Journal: Endoscopy (2004)

Introduction: Coeliac disease (CD) is an immune mediated disease, induced by gluten. Anti-endomysial (EMA) antibodies are widely used in screening for CD. The classical gut lesion in CD is characterized by a flattened small intestinal mucosa with an inflammatory cells infiltratation, increased epithelial cell proliferation and crypt hyperplasia.
Genotype concordance between archival tumor DNA (atDNA) and circulating tumor DNA (ctDNA) in advanced solid malignancies: The Oncopanel Pilot study.
Authors: Hagen F. Kennecke, Kevin Bushell, Colleen E. McGahan, Solomon A. Vandt, Jonathan M. Loree, Ian Bosdet, Lucas Swanson, Liz Starks, Jordan Davidson, Christopher Tan, John Paul McGhie, Bal Johal, Sara Kristina Taylor, Muhammad Zulfiqar, Janessa J. Laskin, Janine Marie Davies, Barbara L. Melosky, Sophie Sun, Aly Karsan, Ryan Morin
Journal: Journal of Clinical Oncology (2016)

1582 Background: ctDNA is a potentially superior means of classifying tumor genotype but predictors of Con with atDNA are not well established. We conducted a prospective multicenter study to determine the feasibility of atDNA genotyping on a Next-Generation Sequencing (NSG) platform and ctDNA genotyping among patients with advanced solid malignancies. ctDNA genotyping was concurrently performed and variables associated with Con were investigated. Methods: Patients at 5 BC Cancer Agency Centers were enrolled over 14 months. atDNA genotype was performed using NSG and high-throughput multiplex amplification of a 27 gene panel (Raindance). ctDNA genotyping was done with Boreal Genomics OnTarget on 4cc plasma from blood collected in Streck tubes processed within 96 hours. Con was determined in “clinical gene” subsets for Colorectal (CR) (KRAS, NRAS, BRAF), Lung (L) (EGFR, KRAS) and Melanoma (M)(BRAF). Results: Of 300 patients, tumor origin was CR (46%), L (28%), M (M) (7.7%), and Other (18%). The number of metastatic sites was 1 in 39% and >1 in 54% and 64% had resected primary tumors. 50% of patients had received systemic or radiation therapy within 3 months (median 18 d of ctDNA) and 48% had ≥1 elevated tumor marker. In multivariate analysis, higher Con was seen in CR compared to L (OR 2.5; 95%CI 1.2, 5.2) and when time between atDNA and ctDNA was ≤1 year versus >1 year (OR 2.4; 95%CI 1.03, 5.5). Con was not affected by # or type of metastasis, receipt of prior therapy, resection of the primary tumor or elevated tumour marker. ctDNA analysis was completed on the initial 181 cases. Conclusions: Concordance between atDNA and ctDNA was lower in L cancer and higher concordance was associated with shorter time interval between surgical and liquid biopsy. It was not associated with extent of metastatic disease and other measured variables. Discordance was more frequently related to variants not found in ctDNA. Updated results for the full cohort will be presented. Clinical trial information: NCT02171286. Colorectal Lung Melanoma p-value KRAS NRAS BRAF EGFR KRAS BRAF Concordance 77% 94% 91% 74% 75% 79% + atDNA - ctDNA 17% 0% 5% 24% 14% 21% - atDNA +ctDNA 6% 6% 4% 2% 11% 0% Overall Concordance 59/83 (71%) 30/57 (53%) 11/14 (79%) 0.043
Responsiveness and minimal important difference of the urticaria control test
Authors: Tatevik Ohanyan, Nicole Schoepke, Bediha Bolukbasi, Martin Metz, Tomasz Hawro, Torsten Zuberbier, Adriane Peveling-Oberhag, Petra Staubach, Marcus Maurer, Karsten Weller
Journal: Journal of Allergy and Clinical Immunology (2017)
Crohn's Disease Derived Mononuclear Cells Exhibit a Dysregulated Cytokine Response upon In-Vitro Exposure to Mycobacterium Avium Subspecies Paratuberculosis (MAP)
Authors: S Sibartie, P Scully, J Keohane, S O'Neill, J O'Mahony, L O'Mahony, F Shanahan
Journal: Endoscopy (2006)

Aims: MAP has been detected in various tissues from Crohn's disease (CD) patients. We evaluated the cellular response to MAP from CD patients and healthy volunteers.
Peripheral Immunophenotyping Identifies Three Subgroups Based on T Cell Heterogeneity in Lupus Patients
Authors: Satoshi Kubo, Shingo Nakayamada, Maiko Yoshikawa, Yusuke Miyazaki, Kei Sakata, Kazuhisa Nakano, Kentaro Hanami, Shigeru Iwata, Ippei Miyagawa, Kazuyoshi Saito, Yoshiya Tanaka
Journal: Arthritis & Rheumatology (2017)

Objective To elucidate the diversity of systemic lupus erythematosus (SLE) based on immunophenotyping. Methods Peripheral blood mononuclear cells were obtained from 143 SLE patients and 49 healthy individuals. Circulating B, T, and dendritic cells were defined using flow cytometric analysis as recommended by the Human Immunology Project Consortium. Based on these results, immunophenotypes were distinguished by principal components analysis (PCA), and cluster analysis was used to classify SLE patients into subgroups. Results The proportions of Treg and follicular helper T (Tfh) cells were higher in SLE patients than in healthy controls, whereas Th1 and Th17 cell proportions did not differ. Proportions of class‐switched memory B cells and IgD–CD27– B cells were increased in SLE patients as well. The largest difference compared to the control group was observed in the proportion of plasmablasts, which was higher in SLE patients and correlated with disease activity as assessed with the British Isles Lupus Assessment Group index. PCA indicated that the immunophenotype of SLE patients consisted of abnormalities of the T and B cell axes. Cluster analysis showed that the SLE patients could be stratified into 3 subgroups (with high proportions of plasmablasts in all groups): patients who did not show the characteristic features (T cell–independent group), patients with a high percentage of Tfh cells (Tfh‐dominant group), and patients with a high percentage of memory Treg cells (Treg‐dominant group). The percentage of patients whose SLE was resistant to treatment was highest among the Tfh‐dominant group. Conclusion Our study indicates that patients with active SLE can be divided into 3 subgroups based on T cell heterogeneity. Further immunophenotyping studies should help elucidate the pathogenesis of SLE and provide important information for the development of new therapies.
SELDI-MS Protein Profiling Differentiates Ovarian From Colon Cell Lines
Authors: AM Lennon, D Stuart, AC Tan, KS Sheahan, DP O'Donoghue, B Brown
Journal: Endoscopy (2004)

Introduction Surface enhanced laser desorption ionisation mass spectrometry (SELDI-MS) is a technique which has been used to study proteomic patterns. The aim of this study was to determine the sensitivity of SELDI-MS in differentiating two different cell lines.
Clinical Utility of Chromosomal Aneusomy in Individuals at High Risk of Lung Cancer
Authors: Anna E. Barón, Severine Kako, William J. Feser, Heather Malinowski, Daniel Merrick, Kavita Garg, Stephen Malkoski, Shannon Pretzel, Jill M. Siegfried, Wilbur A. Franklin, York Miller, Holly J. Wolf, Marileila Varella-Garcia
Journal: Journal of Thoracic Oncology (2017)
Frequency, severity and timing of common adverse events (AEs) with maintenance olaparib in patients (pts) with platinum-sensitive relapsed serous ovarian cancer (PSR SOC).
Authors: Ursula Matulonis, Michael Friedlander, Andreas Du Bois, Charlie Gourley, Ignace Vergote, Gordon J. S. Rustin, Clare L. Scott, Werner Meier, Ronnie Shapira-Frommer, Tamar Safra, Daniela Matei, Anitra Fielding, Emma McMurtry, Stuart Spencer, Helen Mann, David Parry, Jonathan A. Ledermann
Journal: Journal of Clinical Oncology (2015)

5550 Background: Maintenance monotherapy with the PARP inhibitor olaparib prolongs progression-free survival in PSR SOC pts with no adverse impact on HRQoL. BRCAm pts derive greater benefit. Nausea, vomiting, fatigue and anemia are consistently the most common AEs in olaparib trials. Methods: In this randomized, double-blind Phase II trial (NCT00753545), pts received olaparib 400 mg twice daily (capsules; n=136) or placebo (n=128). AEs were graded by CTCAE v3.0; the timing and severity of AEs were analyzed. Results: Olaparib-treated pts most commonly reported early but transient grade (G)1/2 AEs of nausea, vomiting, fatigue and anemia that resolved with supportive treatment without olaparib regimen changes. G>2 AEs were uncommon and manageable with dose interruptions/reductions and supportive treatment. Anemia was the most common G>2 AE. Common AEs were generally reported later for placebo pts. AEs causing discontinuation were uncommon (olaparib, n=9; placebo, n=2). BRCAm pts had a similar AE profile. Conclusions: AEs commonly reported with olaparib are of mostly mild to moderate intensity, transient and manageable without olaparib discontinuation. Clinical trial information: NCT00753545. Nausea Vomiting Fatigue and asthenia Anemia Olaparib Placebo Olaparib Placebo Olaparib Placebo Olaparib Placebo Pts with AE 96 (71) 46 (36) 47 (35) 18 (14) 84 (62) 59 (46) 29 (21) 7 (5) AE instances* 128 58 82 20 114 72 34 8 G1 101 (79) 46 (79) 58 (71) 12 (60) 66 (58) 58 (81) 5 (15) 4 (50) G2 24 (19) 12 (21) 21 (26) 7 (35) 36 (32) 10 (14) 21 (62) 3 (38) G3/4 3 (2) 0 3 (4) 1 (5) 12 (11) 4 (6) 8 (24) 1 (13) Discontinued† 1 (1) 1 (2) 0 0 0 0 0 0 Dose reduced† 5 (4) 0 4 (5) 1 (5) 9 (8) 1 (1) 6 (18) 1 (13) Interrupted† 9 (7) 1 (2) 18 (22) 1 (5) 8 (7) 2 (3) 4 (12) 0 Resolved 102 (80) 46 (79) 80 (98) 17 (85) 68 (60) 35 (49) 23 (68) 6 (75) Treated 57 (45) 10 (17) 19 (23) 3 (15) 5 (4) 3 (4) 24 (71) 2 (25) Median duration, mo (IQR)‡ 2.2 (1, 7) 0.82 (0.1, 2.4) 0.05 (0.03, 0.13) 0.1 (0.03, 0.1) 3.4 (2, 7) 2.8 (1.5, 4.3) 2.4 (1, 6.6) 0.5 (0.3, 1.4) Time to first occurrence, d (IQR) 3 (1, 15) 12 (4, 29) 49 (10, 112) 64 (25, 106) 24 (7, 57) 28 (7, 48) 28 (14, 59) 91 (49, 133) Values are n (%) unless stated. *Includes AEs considered unrelated to treatment; †AE related; ‡Includes intermittent events.
Resectable Clinical N2 Non–Small Cell Lung Cancer; What Is the Optimal Treatment Strategy? An Update by the British Thoracic Society Lung Cancer Specialist Advisory Group
Authors: Matthew Evison, Amelia Clive, Lianne Castle, Helen Powell, Rachel Thomas, Robert Buttery, Vidan Masani, Susan Harden, Doug West, Ian Woolhouse
Journal: Journal of Thoracic Oncology (2017)
Arcuate neuropeptide Y inhibits sympathetic nerve activity via multiple neuropathways
Authors: Zhigang Shi, Christopher J. Madden, Virginia L. Brooks
Journal: Journal of Clinical Investigation (2017)

Obesity increases sympathetic nerve activity (SNA) via activation of proopiomelanocortin neurons in the arcuate nucleus (ArcN), and this action requires simultaneous withdrawal of tonic neuropeptide Y (NPY) sympathoinhibition. However, the sites and neurocircuitry by which NPY decreases SNA are unclear. Here, using designer receptors exclusively activated by designer drugs (DREADDs) to selectively activate or inhibit ArcN NPY neurons expressing agouti-related peptide (AgRP) in mice, we have demonstrated that this neuronal population tonically suppresses splanchnic SNA (SSNA), arterial pressure, and heart rate via projections to the paraventricular nucleus (PVN) and dorsomedial hypothalamus (DMH). First, we found that ArcN NPY/AgRP fibers closely appose PVN and DMH presympathetic neurons. Second, nanoinjections of NPY or an NPY receptor Y1 (NPY1R) antagonist into PVN or DMH decreased or increased SSNA, respectively. Third, blockade of DMH NPY1R reversed the sympathoinhibition elicited by selective, DREADD-mediated activation of ArcN NPY/AgRP neurons. Finally, stimulation of ArcN NPY/AgRP terminal fields in the PVN and DMH decreased SSNA. Considering that chronic obesity decreases ArcN NPY content, we propose that the ArcN NPY neuropathway to the PVN and DMH is pivotal in obesity-induced elevations in SNA.
Number needed to treat II
Authors: P. Sedgwick
Journal: BMJ (2011)

Researchers assessed the efficacy and safety of varenicline, a smoking cessation aid for users of smokeless tobacco. A double blind, placebo controlled, randomised controlled trial was performed. In total, 213 participants were allocated to varenicline and 218 to placebo. Treatment was for 12 weeks, with 14 weeks of follow-up after treatment.1

The primary end point was continuous abstinence from smoking for four weeks at the end of treatment (weeks 9 to 12). Continuous abstinence was achieved by 59% of participants in the varenicline group and 39% in the placebo group, an absolute risk difference of 0.2. The relative risk of continuous abstinence between weeks 9 and 12 for varenicline compared with placebo was 1.60 (95% confidence interval 1.32 to 1.87; P<0.001).

Which one of …