tbuckley/cabot-search huggingface dataset:
Analytical validation of StrandAdvantage solid tumor NGS test.
Authors: Vamsi Veeramachaneni, Shanmukh Katragadda, Minothi Parulekar, Satish Sankaran, Vaijayanti Gupta, Manimala Sen, Manasa B.P., N.S.N Swetha, Smita Agarwal, Goutham HV, Jamuna Yadhav, Suman Kapoor, Gouri Deshpande, Vikram Vitthal, Weiming Shen, Melanie Phooi Nee Yong, Urvashi Bahadur, Preveen Ramamoorthy, Kalyanasundaram Subramanian, Ramesh Hariharan
Journal: Journal of Clinical Oncology (2015)

e12539 Background: Personalized cancer treatment can benefit from targeted deep-sequencing of multiple genes using NGS. The StrandAdvantage test panel assays 212 amplicons (48 genes) spanning hotspot mutations with highest relevance to the treatment of cancer. It is performed using the Illumina TSACP panel. We present results from the analytical validation of this panel performed in two different Strand laboratories located in Bangalore, India and Denver, U.S.A using DNA extracted from fresh tissue, FFPE, commercially available controls and patient samples. Methods: The analytical validation framework addresses accuracy, sensitivity and specificity, limit of detection, precision and reproducibility, using 12-15 independent sequencing runs of about 20 samples each performed in two separate laboratories (Bangalore and Denver). All of the above mentioned StrandAdvantage test performance characteristics were evaluated using DNA and FFPE reference standards from Horizon Diagnostics (Cambridge, UK), Jurkat and MDA-MB-231 cell lines from ATCC, USA. Additionally, SNP concordance was evaluated across 7 HapMap samples from a Utah family, and evaluated against Illumina’s data on the same samples. The assay was further evaluated for its performance on normal and tumor FFPE samples. A limited number of mutations detected in FFPE patient samples were confirmed using Sanger sequencing and ARMS- Scorpion qPCR assay. Limit of detection experiments were performed using the Horizon DNA and FFPE QMRS standards, and various dilutions of cell lines, fresh tissue and FFPE samples. Results: We achieved equivalent performance across different operators, sequencing runs and laboratories in two independent Strand laboratories (Bangalore, India and Denver, U.S.A). The analytical performance shows 98% accuracy, sensitivity and specificity for this assay independently in both laboratories. Precision and reproducibility were established at 99%. The limit of detection of SNPs was set at a conservative 10%, even though the assay detected accurately SNPs at lower frequencies. Conclusions: These data thus demonstrate robust technical performance of the StrandAdvantage solid tumor NGS test and its suitability for adoption in clinical oncology practice.
1-β-D-Arabinofuranosylcytosine-lnduced Chromatid Breakage: Effect of Inhibition of DNA Synthesis&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: W F Benedict, N Rucker, M Karon
Journal: JNCI Journal of the National Cancer Institute (1975)

The frequency of chromatid breakage induced by 1-beta-D-arabinofuranosylcytosine was decreased when hamster cell fibroblasts were treated with chemical agents that interferred with DNA synthesis immediately before addition of the analog. This phenomenon occurred in both the S and G2 phases of the cell cycle.
A randomized trial of amsacrine and rubidazone in 39 patients with acute promyelocytic leukemia.
Authors: P Fenaux, G Tertian, S Castaigne, H Tilly, G Leverger, H Guy, D Bordessoule, R Leblay, E Le Gall, P Colombat
Journal: Journal of Clinical Oncology (1991)

Thirty-nine patients with untreated acute promyelocytic leukemia (APL) were randomly allocated to receive rubidazone (zorubicin) 200 mg/m2/d, days 1 to 4 plus cytarabine (Ara C) 200 mg/m2/d, days 1 to 7 (arm A, 21 patients), or amsacrine (Amsa) 150 mg/m2/d, days 1 to 4 plus Ara C 200 mg/m2/d, days 1 to 7 (arm B, 18 patients). Prophylaxis of disseminated intravascular coagulation was made by platelet transfusions and heparin. In case of leukemic resistance, patients received a second course with 2 days of rubidazone (arm A) or Amsa (arm B) and 3 days of Ara C. Patients who achieved complete remission (CR) received three consolidation courses with the two drugs used for induction and maintenance therapy for 3 years. Two patients in arm A and one in arm B were allografted in first CR. Initial characteristics were similar in both arms. In arm A, 18 patients (86%) reached CR, two had hypoplastic death, and one had leukemic resistance after two courses. In arm B, 12 patients (66%) achieved CR, two had early death (CNS bleeding, one case; ventricular fibrillation, one case), and four had resistant leukemia after two courses. The difference in CR rate between the two arms was not significant. In arm A, disease-free survival (DFS) showed a plateau at 54.3% after 34 months (95% confidence interval [CI], 32.1% to 74.9%), with eight CRs longer than 34 months. In arm B, DFS was significantly shorter (P less than .03), showing a plateau at 16.7% after 38 months (95% confidence interval, 4.7% to 44.6%), and only two prolonged CRs were seen. The difference in DFS remained significant after censoring allografted patients and patients who died in CR (one in arm A, two in arm B). Our results suggest that Amsa-Ara C combinations may be inferior to anthracycline-Ara C combinations in the treatment of APL, because they seem to provide shorter DFS and, possibly, a higher incidence of initial leukemic resistance. However, studies with larger numbers of patients are required.
Abstract 167: Genetic Deletion of p66Shc Adaptor Protein Leads to Increased Myocardial Infarction by Inhibiting RISK and SAFE Prosurvival Pathways
Authors: Alexander Akhmedov, Vincent Braunersreuther, Fabrizio Montecucco, Philip Jakob, Giovanni G Camici, Francois Mach, Thomas F Luescher
Journal: Circulation Research (2013)

Background— Formation of reactive oxygen species (ROS) contributes to many pathophysiological processes. Although ROS production is also involved in some physiological processes, the imbalance between their generation and removal, i.e. oxidative stress, plays a major role in particular in myocardial injury caused by ischemia-reperfusion (I/R). The mammalian Shc locus encodes three Shc isoforms: p46 Shc , p52 Shc and p66 Shc . The p66 Shc is not involved in mitogenic signals as p46 Shc /p52 Shc , but it functions as a critical mediator of intracellular oxidative signal transduction. Various studies relate p66 Shc to cardiovascular disease; however, few data are available on the role of p66 Shc in myocardial I/R. Methods and Results— 8-12-week-old male p66 Shc deficient ( p66 Shc-/- ) mice and corresponding C57Bl/6 wild-type (WT) control mice were subjected in vivo to different durations of ischemia (30, 45 and 60 min) followed by 24h of reperfusion. Infarct size was assessed morphologically and by MRI. After 30 min of ischemia, p66 Shc-/- mice developed markedly larger infarcts as compared to WT. This effect was confirmed by in vivo silencing of p66 Shc prior to I/R. Both genetic deletion and silencing of p66 Shc displayed increased post-ischemic levels of serum cardiac troponin I (cTnI). However, the observed effect on infarct size was limited to 30 min of ischemia since by increasing ischemia duration to either 45 or 60 min infarct size did no longer differ between p66 Shc-/- and WT mice. Moreover, differently from WT, infarct size in p66 Shc-/- was not significantly larger with increasing duration of ischemia (from 30 to 60 min). On the molecular level the observed effect was linked to the inhibition of activation by phosphorylation of protein kinase Akt and transcription factor STAT3 - two key members of prosurvival pathways RISK and SAFE, respectively. Conclusions— Our data suggest that genetic deletion of p66 Shc leads to an increased sensitivity to myocardial infarction with larger infarcts with shorter, but not prolonged ischemia, and that RISK and SAFE prosurvival pathways are involved. Therefore, activation of p66 Shc may provide resistance to ischemia and represent a novel therapeutic target in the early phase of myocardial infarction.
Toxicity, immunogenicity, and tumor radioimmunodetecting ability of two human monoclonal antibodies in patients with metastatic colorectal carcinoma.
Authors: R G Steis, J A Carrasquillo, R McCabe, M A Bookman, J C Reynolds, S M Larson, J W Smith, J W Clark, V Dailey, S Del Vecchio
Journal: Journal of Clinical Oncology (1990)

Two human immunoglobulin M (IgM) monoclonal antibodies (MoAbs), 16.88 and 28A32, which react with cytoplasmic (28A32 and 16.88) or cell surface (28A32) determinants on human colon carcinoma cells, were administered intravenously to 26 patients with metastatic colorectal carcinoma to determine if they could localize to sites of metastatic disease, if they had any antitumor or toxic effects, and to determine whether they would elicit an antihuman MoAb response. Serial scans showed tumor uptake of radioisotope in 12 of 16 patients receiving 131I-labeled 28A32 and in nine of 12 patients receiving 131I-labeled 16.88. No antitumor effects were seen with either antibody. No antibody-related toxic effects were observed following administration of 16.88, but two patients developed localized urticarial reactions following injection with antibody 28A32. No patient developed an antibody response to 16.88. Anti-28A32 reactivity was found in five of 12 (42%) normal sera and in seven of 23 (30%) patients before receiving any antibody. Following administration of 28A32, a low titer (1:10 dilution) of anti-28A32 developed in four patients with no preexisting antibody, a decrease in the preexisting titer was seen in three other patients, the titer remained constant in one patient, and no anti-28A32 was ever detected in six patients. In most cases, anti-28A32 activity was lost at dilutions greater than 1:10 and did not appear to affect antibody half-life in the serum or whole body retention of the antibody. We conclude that these human IgM MoAbs are capable of localizing at sites of disease in vivo, are nontoxic, and are poorly immunogenic in humans. Further studies to determine the specificity of targeting and to improve the delivery of antibody to sites of tumor are indicated.
Tackling inequality: get them while they're young
Authors: C. Hertzman, A. Siddiqi, E. Hertzman, L.G. Irwin, Ziba Vaghri, T.A.J. Houweling, R. Bell, A. Tinajero, M. Marmot
Journal: BMJ (2010)

A good start in life is the key to reducing health and social inequalities. Clyde Hertzman and colleagues argue that governments in rich and poor countries should invest more in programmes to support early child development.
Evaluation of significance of endoscopic mucosal resection (EMR) in early esophageal cancer
Authors: T. Yoshii, S. Tamai, O. Motohashi, K. Yonemitsu, A. Kiyohashi, S. Takagi, N. Nakayama, Y. Murata
Journal: Journal of Clinical Oncology (2006)

4088 Background: Radical surgery for esophageal cancer is very invasive. Endoscopic mucosal resection (EMR), which conserves the esophagus, is a minimally invasive and attractive therapeutic modality for early stage esophageal cancer. However, when the tumor reaches the deep mucosal or submucosal layer (“T1b” according to TNM classification), the incidence of lymph node metastasis (LNM) increases up to 10–50%. Therefore, the indications of EMR have to be clarified. Methods: Retrospective analysis was performed regarding the clinical course of 41 patients who were diagnosed as having cT1bN0M0 esophageal cancer and underwent EMR between 1994 and 2004 at our hospital. Statistical analysis was performed by the log-rank and Kaplan-Meier methods. Results: Thirty nine patients were selected and followed up without any additional therapy after obtaining written informed consent. Twenty patients (51%) had multiple primary cancers, 10 died, and 29 are still alive. MST of the dead patients was 22 months, and 7 of them (70%) died of advanced multiple primary cancers, while death was cause specific in only one case (due to LNM). The survival curves showed no significant differences between the patients with early multiple primary cancers and those without multiple cancers patients (MST = 72 months, p &lt; 0.7784). In most of the dead patients and 23 of the surviving patients, the local lesion was well controlled without any recurrence. Conclusions: Many patients with early esophageal cancer who underwent EMR tended to die of multiple primary cancers. When the patient had early multiple primary cancers, the prognosis was not different from those without such cancer and the local lesion was well controlled. We concluded that EMR is a very useful therapeutic modality for local control as it is minimally invasive, especially in patients with multiple primary cancers. No significant financial relationships to disclose.
Two Phenotypes Are Identified by Cluster Analysis in Early Inflammatory Back Pain Suggestive of Spondyloarthritis: Results From the DESIR Cohort
Authors: Félicie Costantino, Philippe Aegerter, Maxime Dougados, Maxime Breban, Maria‐Antonietta D'Agostino
Journal: Arthritis & Rheumatology (2016)

To determine whether disease manifestations at baseline would combine according to distinguishable ordered phenotypes in patients with early inflammatory back pain (IBP) suggestive of spondyloarthritis (SpA).Baseline clinical and demographic characteristics as well as imaging features and biologic data on patients included in the French multicenter Devenir des Spondyloarthropathies Indifferérenciées Récentes cohort were analyzed by multiple correspondence analysis and cluster analysis to identify subgroups of patients based on shared characteristics.Cluster analysis allowed us to classify the 679 patients with no missing data into 2 major groups-one with a predominance of isolated axial manifestations and the other with associated peripheral symptoms. The application of the same analysis to selected subsets of the cohort, such as HLA-B27-positive and -negative patients and patients fulfilling the Assessment of SpondyloArthritis international Society classification criteria for axial SpA, resulted again in an optimal division of the samples into 2 recurrent clusters of patients similar to those observed in the whole cohort.Cluster analysis of SpA manifestations among patients with early IBP highly suggestive of SpA allowed us to clearly identify at baseline 2 different clinical phenotypes-one with predominant axial manifestations and the other with predominant peripheral manifestations. Ongoing follow-up will allow us to determine whether these clusters correspond to different patterns of disease severity.
Prospective evaluation of carbonic anhydrase IX (CAIX) as a molecular marker in metastatic renal cell carcinoma
Authors: T. Klatte, N. Zomorodian, F. F. Kabbinavar, A. S. Belldegrun, A. J. Pantuck
Journal: Journal of Clinical Oncology (2007)

5112 Background: CAIX is an important molecular marker of survival and response to immunotherapy in patients with metastatic renal cell carcinoma (RCC). The purpose of this study was to prospectively evaluate the performance of CAIX in patients with metastatic RCC. Methods: This study accrued 32 consecutive patients who were treated for metastatic clear cell RCC between January 2004 and May 2006. Immunohistochemical staining of the primary tumor was performed using the mouse monoclonal antibody MN-75. Patients were stratified into two groups: high CAIX expression (&gt;85%) and low CAIX expression (=85%) according to the percentage of cells staining positive for CAIX. Study endpoints included disease-specific survival time (DSS) and response to treatment according to RECIST criteria. Results: Four (12.5%), 21 (65.6%), and 7 patients (21.9%) were classified into low risk, intermediate risk, and high risk groups according to the University of California Integrated Staging System (UISS). Twenty (62.5%) of the 32 patients had high CAIX expression. The median follow-up was 11.4 months. Patients with low CAIX expression had significantly worse prognosis than patients with high CAIX expression (median survival: 15.2 months vs. not reached, p=0.01, 1-year DSS rate: 63% vs. 83%) and a 3.9 fold increased risk of death from RCC (95% CI, 1.2–12.7). All 4 patients in the low risk UISS group had high CAIX expression, and all were alive at 1 year. Nine patients received high dose IL-2 based immunotherapy, including 8 who had high CAIX expression, and a 1-year DSS rate of 87.5%. Of the patients expressing high CAIX, 3 (37.5%) were responders to IL-2 including 1 partial and 2 complete responses, 3 (37.5%) exhibited stable disease and 2 (25.0%) progressed during treatment. Conclusions: The results of this first prospective study of CAIX in metastatic RCC confirm that high CAIX expression is associated with better survival and enhanced response to IL-2 based immunotherapy. Patients with high CAIX expression, specifically those with low risk RCC, should be considered candidates to receive immunotherapy, whereas patients with low CAIX expression or in higher risk groups may be better candidates for targeted or other experimental therapy. No significant financial relationships to disclose.
Influence of IL-1 RA expression in ascites on overall survival (OS) of advanced ovarian cancer (OC) patients (pts)
Authors: A. Mustea, J. Sehouli, D. Koensgen, C. Pirvulescu, E. I. Braicu, M. Hauschild, P. Sun, W. Lichtenegger
Journal: Journal of Clinical Oncology (2005)

9643 Background: Interleukin-1β (IL-1) and IL-1 RA are known to be critically involved in ovarian carcinogenesis. There are limited data on the expression of IL-1 β and RA in ascites in pts with OC. The aim of this study was to analyse the prognostic value of the expression of IL-1 β and RA in ascites of patients with OC. Methods: In a prospective study from 2001 to 2003, 33 pts with primary and 20 with recurrent OC and 50 women with benign gynaecological diseases as a control group (CG) from Charite, Department of Gynaecology and Obstetrics, Berlin were enrolled. IL-1 β and RA levels in ascites were analysed by ELISA technique. Results: The median age of the pts was 55.6 years (range 19–80) in the OC group and 40 years (range, 15–89) in CG. The median follow-up period was 26 (range, 1–42) months. The concentrations of IL-1β and IL-1 RA in ascites were significantly increased in pts with OC in comparison to CG, for both cytokines (p<0.0001). The IL-1β level in ascites correlated significantly with the histological grading (p=0.038). IL-1 RA level in ascites was correlated with FIGOstage (p=0.049). Using Kaplan-Meier method and long-rank test pts with low level of IL-1 RA in ascites was associated with a longer median OS (34.6 vs. 17 months, p=0.01) and progression free survival (PFS): 24.6 vs.12.8 months(p=0.008) in comparison with pts with high level of IL-1 RA in ascites. Application of multivariate Cox regression analysis showed IL-1 RA expression in ascites to be an independent prognostic factor for OS (p=0.04). Conclusions: The data suggest that lower expression of IL-1 RA in ascites correlated significant with improved clinical outcome in pts with OC. IL-1 RA may have important role in the tumorgenesis of OC and lead prognostic information. No significant financial relationships to disclose.
A mouse model recapitulating human monoclonal heavy chain deposition disease evidences the relevance of proteasome inhibitor therapy
Authors: Amélie Bonaud, Sébastien Bender, Guy Touchard, Corinne Lacombe, Nivine Srour, Laurent Delpy, Christelle Oblet, Anne Druilhe, Nathalie Quellard, Vincent Javaugue, Michel Cogné, Frank Bridoux, Christophe Sirac
Journal: Blood (2015)
Requirements and standards facilitating quality improvement for reporting systems in gastrointestinal endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement
Authors: Michael Bretthauer, Lars Aabakken, Evelien Dekker, Michal Kaminski, Thomas Rösch, Rolf Hultcrantz, Stepan Suchanek, Rodrigo Jover, Ernst Kuipers, Raf Bisschops, Cristiano Spada, Roland Valori, Dirk Domagk, Colin Rees, Matthew Rutter
Journal: Endoscopy (2016)

To develop standards for high quality in gastrointestinal (GI) endoscopy, the European Society of Gastrointestinal Endoscopy (ESGE) has established the ESGE Quality Improvement Committee. A prerequisite for quality assurance and improvement for all GI endoscopy procedures is state-of-the-art integrated digital reporting systems for standardized documentation of the procedures. The current paper describes the ESGE's viewpoints on the requirements for high-quality endoscopy reporting systems in GI endoscopy. <b>Recommendations</b> <b>1</b> Endoscopy reporting systems must be electronic. <b>2</b> Endoscopy reporting systems should be integrated into hospitals' patient record systems. <b>3</b> Endoscopy reporting systems should include patient identifiers to facilitate data linkage to other data sources. <b>4</b> Endoscopy reporting systems shall restrict the use of free-text entry to a minimum, and be based mainly on structured data entry. <b>5</b> Separate entry of data for quality or research purposes is discouraged. Automatic data transfer for quality and research purposes must be facilitated. <b>6</b> Double entry of data by the endoscopist or associate personnel is discouraged. Available data from outside sources (administrative or medical) must be made available automatically. <b>7</b> Endoscopy reporting systems shall facilitate the inclusion of information on histopathology of detected lesions, patient satisfaction, adverse events, and surveillance recommendations. <b>8</b> Endoscopy reporting systems must facilitate easy data retrieval at any time in a universally compatible format. <b>9</b> Endoscopy reporting systems must include data fields for key performance indicators as defined by quality improvement committees. <b>10</b> Endoscopy reporting systems must facilitate changes in indicators and data entry fields as required by professional organizations.