tbuckley/cabot-search huggingface dataset:
Comparison of plasma microRNAs with CTCs and PSA in patients treated on SWOG S0925, a randomized phase II study of androgen deprivation combined with cixutumumab versus androgen deprivation alone for patients with new metastatic hormone-sensitive prostate cancer.
Authors: Heather H. Cheng, Hongli Li, Celestia S. Higano, Catherine M. Tangen, Neeraj Agarwal, James Yan, Nicholas J. Vogelzang, Maha Hussain, Ian Murchie Thompson, Muneesh Tewari, Evan Y. Yu
Journal: Journal of Clinical Oncology (2014)

5017 Background: Circulating, blood-based microRNAs (miRNAs), like circulating tumor cells (CTCs), are promising prostate cancer biomarker candidates. However, circulating miRNAs have yet to be examined in prospective clinical trials. Here, we examine the correlation between baseline plasma miRNAs and CTCs with 7-month PSA (previously shown to be strongly correlated with overall survival in SWOG 9346) in patients from SWOG 0925. Methods: Plasma and CTCs were collected prior to initiation of androgen deprivation (AD) from patients on SWOG 0925. miRNA was extracted and measured from plasma using miRCURY RNA Isolation kit and miRNA Ready-to-Use PCR, Human panel I, V1.M qRT-PCR arrays (Exiqon). CTC measurements were performed using the CellSearch® platform (Veridex). Results: Correlation between miRNA cycle threshold and CTCs are shown (Table). Baseline plasma miR-375 levels were associated with stratified 7-month PSA response (≤0.2, 0.2 to ≤4.0, or >4.0, P=0.0071, Friedman test). Using ROC curve analysis, there was no significant difference between baseline miR-375 and baseline CTC in predicting 7-month PSA response (≤0.2 vs. >0.2). Conclusions: Baseline plasma miR-141, miR-200a, miR-200c and miR-375 levels were significantly correlated with baseline CTC count. Baseline plasma miR-375 was similar to baseline CTCs in ability to predict 7-month PSA in a prospective, multi-center clinical trial. Correlation of baseline miRNA (cycle threshold) and CTC counts. MicroRNA N Spearman correlation 95% CI p-value miR-141 35 -0.60 -0.78 to -0.34 0.0001 miR-200a 31 -0.51 -0.73 to -0.19 0.0035 miR-200c 36 -0.34 -0.59 to -0.01 0.0447 miR-210 35 -0.18 -0.48 to 0.16 0.3123 miR-375 36 -0.46 -0.68 to -0.15 0.0051
Use of Cobas 4800 BRAF mutation test for the analysis of BRAF V600 mutations in cytological samples (CS) from metastatic melanoma (MM).
Authors: Salvador Martin-Algarra, Tania Labiano, Jose Ignacio Echeveste, Nerea Gomez, Myriam Montañana, Mercedes Aguirre, Mari­a Eugenia Echarri, Miguel F. Sanmamed, Alfonso Gurpide, Jose Luis Perez-Gracia, Miguel A. Idoate, Maria D. Lozano
Journal: Journal of Clinical Oncology (2012)

8572 Background: Vemurafenib is currently the most active first-line treatment in MM patients that harbor BRAF-V600E mutations. The Cobas 4800 BRAF V600 Mutation Test is an FDA-approved, CE-marked test that identifies formalin-fixed-paraffin-embedded samples (FFPE) carrying the BRAF V600E mutation. Fine needle aspirates are frequently the only samples available in MM patients, but the use of CS has not been validated in this platform. We have evaluated the capability to identify BRAF-V600E mutations in CS of MM with the Cobas 4800 BRAF Mutation Test, and results have been compared to the conventional Sanger direct sequencing method. Methods: BRAF mutations have been studied in 117 samples from 98 MM patients with the conventional Sanger method: 37 (32%) FFPE and 80 (68%) CS. DNA was extracted from 4-micron sections in FFPE and from stained smears in CS. All CS contained &gt;50% of tumor cells. In a second step, 57 out of the 117 samples have been studied using Cobas (25 CS and 32 FFPE). In CS, Nucleospin Tissue (Macherey-Nagel) DNA extraction was used in 17 cases and the Cobas procedure in 8. FFPE and CS paired samples were available in 9 patients. Results were compared using the Kappa coefficient. Results: There was 93% (53/57) agreement between Cobas and direct sequencing. All V600E+ cases were detected with both methods. Four V600R+ cases were negative using Cobas. Mean DNA concentrations using Nucleospin and Cobas procedures were 55.20 ng/µl and 11.37 ng/µl respectively. Concordance using Cobas in FFPE and CS paired samples was 100%. The table shows the results with Cobas and direct sequencing in 25 CS. One V600R+ case was not detected with Cobas. Conclusions: The Cobas 4800 BRAF Mutation Test results using CS containing &gt;50% of tumor cells are identical to those obtained with FFPE. In our experience, DNA concentrations from CS with the Cobas method are lower than those obtained with Nucleospin procedure. These results provide a strong rationale for a larger validation study. [Table: see text]
Single- versus multiple-item assessment of quality of life in patients with advanced cancer
Authors: S. H. Bush, H. A. Parsons, J. L. Palmer, R. Chacko, Z. Li, C. Scott, E. Bruera
Journal: Journal of Clinical Oncology (2009)

e20528 Background: The main objective of palliative cancer care is to improve quality of life (QOL). As multiple dimensions impact on the construct of QOL, multi-dimensional instruments are usually used in its measurement. These are time consuming and burdensome for repeated use. Recent authors have suggested that brief single-item global assessments can provide a reliable measure of QOL. We assessed the performance of the Edmonton Symptom Assessment System ‘feeling of well-being’ item (ESAS WB) using the Functional Assessment of Cancer Therapy - General (FACT-G) instrument as a gold standard. Methods: After obtaining IRB approval, we reviewed the data from 213 advanced cancer patients who had participated in six studies from March 2006 to June 2008 and determined the level of association between baseline ESAS WB and FACT-G total score and subscale domains (Physical (Pwb), Social/Family (Swb), Emotional (Ewb), and Functional (Fwb) Well-Being) and also the 9 ESAS symptom intensity scores using Spearman correlation coefficients. We also calculated the change between the baseline (T1) and second (T2) observations of ESAS WB and of FACT-G total score and determined their level of association using a Pearson correlation coefficient. In addition, we predicted the change in FACT-G as predicted by the change in ESAS WB score using regression analysis. Results: Mean age was 60 (SD 12) years and 48% were female. At T1, the Spearman correlation coefficient of ESAS WB and FACT-G was -0.48 (p&lt;0.0001). Spearman correlation coefficients for ESAS WB and FACT-G subscale domains and ESAS symptom intensity scores were also highly significant (p&lt;0.0001) for all physical and emotional symptoms (other than p=0.003 for nausea) except for FACT Swb (p=0.08). The Pearson correlation coefficient for difference between T1 and T2 in ESAS WB and FACT-G for 146 patients was -0.36 (p&lt;0.0001). The regression analysis was highly significant (p&lt;0.0001). The change in ESAS WB corresponding to FACT-G published minimally important difference (MID) was -0.24 for 3, -1.55 for 5, and -2.87 for 7, respectively. Conclusions: ESAS WB is a practical instrument for clinical use and best reflects the Pwb, Ewb and Fwb domains of FACT-G as compared to Swb. No significant financial relationships to disclose.
Osteopetrosis
Authors: Jakub Tolar, Steven L. Teitelbaum, Paul J. Orchard
Journal: New England Journal of Medicine (2004)

This review of the mechanism of osteopetrosis incriminates molecular defects in osteoclasts as the cause of the imbalance between bone formation by osteoblasts and bone resorption by osteoclasts. Numerous kinds of defects of osteoclast function can cause osteopetrosis in experimental animals, but only one class of defect — the inability to acidify — has been identified in osteopetrosis in humans.
Effectiveness in Predicting the Response and Outcome with Three Prognostic Scoring Systems in Pediatric CML CP on Upfront Imatinib
Authors: Ganta Ranga Raman, Srividya Nasaka, Sadashivudu Gundeti, Vijay Gandhi Linga, Narendra Anukonda, Kkv krishna Mani, Laxmi Srinivas
Journal: Blood (2014)
Detection of colorectal neoplasia associated K-Ras mutations in human urine
Authors: D. E. Brenner, Y. Su, D. P. Normolle, S. Syngal, R. Bresalier, N. Marcon, J. Baron, T. Block
Journal: Journal of Clinical Oncology (2006)

1005 Background: Since colorectal neoplasia-associated genes have been detected in human blood, we hypothesized that small DNA fragments containing genetic mutations associated with colorectal neoplasias are filtered and excreted in the urine. If so, genes associated with colorectal cancer will be detected in the urine. K-ras mutations are commonly associated with colorectal neoplasia and do not occur in the urinary tract. Methods: K-ras mutation detection: 200 microl of urine was extracted with guanidine thiocyanate and purifed using a Wizard DNA isolation kit. Codon 12 K-ras mutation detection methods–1: restriction enriched PCR, 20 cycles, with primers that amplify both wild type and mutated DNA but with an artificial BstNI site at the 5’ end of the amplified product (&gt;2 K-ras copies per assay); 2: Peptide nucleic acid clamping real time PCR (&gt;15 K-ras copies per assay). Human subjects: Training set = 20 patients with known K-ras mutations in colorectal cancer tissue. Test set = blinded urine samples from colorectal adenocarcinoma (N=48), adenoma (N=31), hyperplastic polyp (N=12) and endoscopically normal colon and rectum (N=60). Results: 1. Human urine contains 150–250 base pair DNA fragments derived from the circulation. These fragments can be readily distinguished from high molecular weight DNA from sloughed urinary tract cells. 2. Training set for K-ras detection (tissue confirmed K-ras mutations): Serum 6/20 (30%), Plasma (11/20 (55%), Urine: 18/20 (90%), (p&lt;0.15 for plasma, p&lt;0.001 for serum). 3. Test set (blinded): a. &gt;2 copies of mutated K-ras genes were detected in: 16/48 (33%) adenocarcinomas; 23/31 (74%) adenomas; 5/12 (42%) hyperplastic polyps, and 19/60 (31%) non-neoplasia controls. b. &gt;15 copies of mutated K-ras genes were detected in: 12/48 (25%) adenocarinomas; 15/31 (48%) adenomas; 3/12 (25%) hyperplastic polyps, and 11/60 (18%) non-neoplasia controls. Conclusions: Small DNA fragments in human urine contain K-Ras mutations identical to those found in colorectal cancer DNA. The sensitivity for detection of K-ras mutations in urine appears equivalent or superior to K-ras mutation detection in feces or serum. DNA mutations from systemic epithelial neoplasias may be detected in filtered urinary DNA fragments and may be useful for early detection of neoplasia. No significant financial relationships to disclose.
IMPACT OF GENDER ON OUTCOMES AMONG PATIENTS WITH ACUTE CORONARY SYNDROME UNDERGOING PRIMARY PERCUTANEOUS CORONARY INTERVENTION IN SOUTHEAST ASIA
Authors: Paramaporn Suttirut, Sowitchaya Panthong, Veraprapas Kittipibul, Vorarit Lertsuwunseri, Suphot Srimahachota, Aekarach Ariyachaipanich
Journal: Journal of the American College of Cardiology (2017)
Hyperdiploidy Is Rare in Patients with AL Amyloidosis – Identification of Major Cytogenetic Groups in Early Monoclonal Plasma Cell Disorders.
Authors: Tilmann Bochtler, Ute Hegenbart, Christiane Heiss, Axel Benner, Stephanie Pschowski-Zuck, Désirée Kirn, Kai Neben, Marion Moos, D. Hose, Claus R Bartram, Anthony D. Ho, Hartmut Goldschmidt, Anna Jauch, Stefan Schonland
Journal: Blood (2009)
COMPARISON OF VERAPAMIL VERSUS HEPARIN THERAPY ON PROCEDURAL SUCCESS DURING TRANSRADIAL CORONARY PROCEDURES (VERMUT STUDY)
Authors: Matteo Tebaldi, Simone Biscaglia, Carlo Tumscitz, Francesco Gallo, Giosafat Spitaleri, Annamaria Del Franco, Gianluca Campo
Journal: Journal of the American College of Cardiology (2017)
Analyzing the Stepwise Developmental Pathway From ES/IPS Cells to Functional Mature Erythrocytes.
Authors: Akira Niwa, Tomoki Fukatsu, Katsutsugu Umeda, Itaru Kato, Hiromi Sakai, Tatsuya Morishima, Keisuke Okita, Shinya Yamanaka, Toshio Heike, Tatsutoshi Nakahata
Journal: Blood (2009)
Genetics and Genomics of Congenital Heart Disease
Authors: Samir Zaidi, Martina Brueckner
Journal: Circulation Research (2017)

Congenital heart disease is the most common birth defect, and because of major advances in medical and surgical management, there are now more adults living with congenital heart disease (CHD) than children. Until recently, the cause of the majority of CHD was unknown. Advances in genomic technologies have discovered the genetic causes of a significant fraction of CHD, while at the same time pointing to remarkable complexity in CHD genetics. This review will focus on the evidence for genetic causes underlying CHD and discuss data supporting both monogenic and complex genetic mechanisms underlying CHD. The discoveries from CHD genetic studies draw attention to biological pathways that simultaneously open the door to a better understanding of cardiac development and affect clinical care of patients with CHD. Finally, we address clinical genetic evaluation of patients and families affected by CHD.
CLINICAL CHARACTERISTICS AND IN-HOSPITAL MORTALITY OF VERY ELDERLY PATIENTS WITH CARDIOVASCULAR SHOCK IN JAPAN: THE RESULTS FROM JAPANESE CIRCULATION SOCIETY SHOCK REGISTRY
Authors: Ken Onitsuka, Masahiro Mohri, Yasushi Ueki, Satoru Suwa, Hiroshi Takahashi, Yohei Hokama, Nobuhiro Tanaka, Toshiaki Kadokami, Tetsuya Matoba, Rei Fukuhara, Tsukasa Yagi, Eizo Tachibana, Naohiro Yonemoto, Ken Nagao
Journal: Journal of the American College of Cardiology (2017)
Use of intensive antibiotic prophylaxis and a chemotherapy only T-cell depleted preparative regimen (prep reg) as a pilot study in haploidentical (haplo) transplant (tp) for treatment of pts with advanced leukemia
Authors: J. L. Gajewski, C. Ippoliti, S. A. Giralt, R. Jones, J. McMannis, E. Shpall, I. Khouri, C. Hosing, R. E. Champlin, M. L. Donato
Journal: Journal of Clinical Oncology (2004)

6645 Background: Haploidentical tp offers the option for allogeneic tp because almost everyone has a parent or child who can serve as a donor. Methods: We present preliminary data of haplo tp for 11 pts using a chemotherapy only prep reg of 140 mg/m2 Melphalan on day –8; 10 mg/kg Thiotepa on day –7; 160 mg/m2 Fludarabine on days -6,-5,-4,-3; 1.5 mg/kg of rabbit ATG/day days -6, -5, -4, -3 and T-cell depleted product with < 1 x 104 CD3+ T-cells/kg recipient body weight and > 1 x 107 CD34+/kg recipient body weight to treat pts with advanced leukemia. Pts received: intensive PCP prophylaxis with bactrim and pentamidine prior to tp and during pancytopenia; CMV prophylaxis with valcyte and foscarnet while pancytopenic; and with ambisone for fungus. The last 3 pts enrolled were treated with cancidas prophylactically. Results: 9 of 11 pts engrafted (82%). 2 pts had protocol deviations and primary graft failure - 1 survived disease free and 1 relapsed. Median time to engraftment was 14 days (range, 9–26) to 500 neutrophils. 3 pts are alive without disease recurrence at 9, 10, and 13 months post-tp. 4 pts had disease progression or relapse at a median of 3 months post-tp (range 2–10 months). 4 pts died within 6 months post-tp (2 relapse and 2 non-relapse deaths). 2 additional pts died of relapse at 10 and 11 months. 2 pts developed grade 1 acute graft-versus-host disease (GVHD) and all surviving pts have limited chronic GVHD. None of the 3 pts who died after 100 days post-tp had chronic GVHD. Conclusions: This report for haplo tp demonstrates that a chemotherapy only prep reg achieved a high rate of engraftment. Infectious complications were minimal. Given the refractory nature of the pts treated, there is a 56% estimated survival at 6 months in pts who engrafted. If results are sustained in a larger study, haplo tp may offer hope of allogeneic tp for every individual needing such therapy. No significant financial relationships to disclose.
Mechanism of Marked Reduction In the Severity of Graft-Versus-Host Disease by Reduced-Intensity Conditioning In Murine MHC-Haploidentical BMT Model
Authors: Takayuki Inoue, Kazuhiro Ikegame, Satoshi Yoshihara, Katsuji Kaida, Kyoko Taniguchi, Hiroya Tamaki, Tatsuya Fujioka, Masaya Okada, Ruri Kato, Yoko Yamamoto, Toshihiro Soma, Hiroyasu Ogawa
Journal: Blood (2010)
INSUFLACIÓN DE DIÓXIDO DE CARBONO VERSUS AIRE AMBIENTE EN COLONOSCOPIA CON SEDACIÓN PROFUNDA: ESTUDIO COMPARATIVO EN UN HOSPITAL DE TERCER NIVEL
Authors: M San Juan Acosta, C De Gracia Fernández, O Nogales Rincón, J García Lledó, L Perez Carazo, B Merino Rodríguez, C Jimeno María, A Ferrando, J Garrido Ramírez, C González Asanza
Journal: Endoscopy (2015)

La insuflación con dióxido de carbón (CO2) es una alternativa a la insuflación con aire para distender el colon durante la colonoscopia. Su rápida absorción y eliminación por el pulmón puede explicar mejor tolerancia, y disminución del dolor abdominal post-colonoscopia.
Effects of gefitinib and vandetanib on human equilibrative nucleoside transporter 1 and on gemcitabine cytotoxicity.
Authors: Vijaya L. Damaraju, Tara Scriver, Delores Mowles, Carol E Cass, Michael B. Sawyer
Journal: Journal of Clinical Oncology (2013)

2546 Background: Combination chemotherapy with tyrosine kinase inhibitors (TKIs) and gemcitabine has been attempted with little added benefit to patients. We hypothesized that TKIs that were designed to bind to ATP pockets of growth factor tyrosine kinases also bind to proteins that recognize nucleosides, thereby potentially interfering with gemcitabine pharmacology. Methods: Interaction of TKIs with human nucleoside transporters (NTs) was studied using recombinant NTs produced in yeast. Effects of TKIs on uridine transport, gemcitabine transport and accumulation, regulation of NT activity and cytotoxicity with and without gemcitabine were evaluated in human A549 lung cancer cells. Results: In yeast, vandetanib inhibited two equilibrative NTs (hENT1, hENT2) and three concentrative NTs (hCNT1, hCNT2, hCNT3) with the greatest inhibition seen with hENT1 whereas gefitinib strongly inhibited hENT1 and hCNT1 only. In A549 cells, which possess major hENT1 and minor hENT2 activities, [ 3 H]uridine uptake was inhibited by vandetanib and gefitinib with IC 50 values of 16 ± 4 and 5 ± 0.3µM, respectively. Both TKIs also inhibited [ 3 H]gemcitabine transport and accumulation in A549 cells. hENT1 protein levels were decreased during exposures to vandetanib or gefitinib for 24 hours, and cytotoxicity was greatest when gemcitabine was given prior to vandetanib or gefitinib. Conclusions: Vandetanib and gefitinib inhibited human NTs, especially hENT1, resulting in reduced intracellular gemcitabine accumulation. Gefitinib or vandetanib levels achieved in plasma and tumor tissues are sufficient to inhibit hENT1 activity. Because TKIs can block uptake of nucleoside chemotherapy drugs in cultured cancer cells, attention must be paid to TKIs and nucleoside pharmacokinetic properties when scheduling TKIs and nucleoside chemotherapy.
ASSOCIATION OF STRESS TEST RISK CLASSIFICATION WITH HEALTH STATUS CHANGE AFTER CHRONIC TOTAL OCCLUSION PCI: INSIGHTS FROM THE OPEN-CTO REGISTRY
Authors: Adam Christopher Salisbury, John Saxon, James Sapontis, Kensey Gosch, William Lombardi, Dimitrios Karmpaliotis, Jeffrey Moses, Mohammed Qintar, Ajay Kirtane, John Spertus, David Cohen
Journal: Journal of the American College of Cardiology (2017)
Epigenetic landscapes reveal transcription factors that regulate CD8+ T cell differentiation
Authors: Bingfei Yu, Kai Zhang, J Justin Milner, Clara Toma, Runqiang Chen, James P Scott-Browne, Renata M Pereira, Shane Crotty, John T Chang, Matthew E Pipkin, Wei Wang, Ananda W Goldrath
Journal: Nature Immunology (2017)
New Molecular Assay for the Proliferation Signature in Mantle Cell Lymphoma Applicable to Formalin-Fixed Paraffin-Embedded Biopsies
Authors: David W. Scott, Pau Abrisqueta, George W. Wright, Graham W. Slack, Anja Mottok, Diego Villa, Pedro Jares, Hilka Rauert-Wunderlich, Cristina Royo, Guillem Clot, Magda Pinyol, Merrill Boyle, Fong Chun Chan, Rita M. Braziel, Wing C. Chan, Dennis D. Weisenburger, James R. Cook, Timothy C. Greiner, Kai Fu, German Ott, Jan Delabie, Erlend B. Smeland, Harald Holte, Elaine S. Jaffe, Christian Steidl, Joseph M. Connors, Randy D. Gascoyne, Andreas Rosenwald, Louis M. Staudt, Elias Campo, Lisa M. Rimsza
Journal: Journal of Clinical Oncology (2017)

Purpose Mantle cell lymphoma is an aggressive B-cell neoplasm that displays heterogeneous outcomes after treatment. In 2003, the Lymphoma/Leukemia Molecular Profiling Project described a powerful biomarker—the proliferation signature—using gene expression in fresh frozen material. Herein, we describe the training and validation of a new assay that measures the proliferation signature in RNA derived from routinely available formalin-fixed paraffin-embedded (FFPE) biopsies. Methods Forty-seven FFPE biopsies were used to train an assay on the NanoString platform, using microarray gene expression data of matched fresh frozen biopsies as a gold standard. The locked assay was applied to pretreatment FFPE lymph node biopsies from an independent cohort of 110 patients uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Seventeen biopsies were tested across three laboratories to assess assay reproducibility. Results The MCL35 assay, which contained a 17-gene proliferation signature, yielded gene expression of sufficient quality to assign an assay score and risk group in 108 (98%) of 110 archival FFPE biopsies. The MCL35 assay assigned patients to high-risk (26%), standard-risk (29%), and low-risk (45%) groups, with different lengths of overall survival (OS): a median of 1.1, 2.6, and 8.6 years, respectively (log-rank for trend, P &lt; .001). In multivariable analysis, these risk groups and the Mantle Cell Lymphoma International Prognostic Index were independently associated with OS ( P &lt; .001 for both variables). Concordance of risk assignment across the three independent laboratories was 100%. Conclusion The newly developed and validated MCL35 assay for FFPE biopsies uses the proliferation signature to define groups of patients with significantly different OS independent of the Mantle Cell Lymphoma International Prognostic Index. Importantly, the analytic and clinical validity of this assay defines it as a reliable biomarker to support risk-adapted clinical trials.
HEALTH INSURANCE RELATED DISPARITIES IN REPERFUSION AND MORTALITY FOR PATIENTS WITH ST SEGMENT ELEVATION MYOCARDIAL INFARCTION IN SERGIPE, BRAZIL
Authors: A.S. Jose, F.H. Barreto, Laís Costa Souza Oliveira, Jeferson Cunha Oliveira, Ikaro Daniel De Carvalho Barreto, Larissa Andreline Maia Arcelino, José Eduardo Pereira Ferreira, José Teles De Mendonça, Rafael Barreto, Enilson Moraes, Thiago Nascimento, Luiz Flávio Prado, Fabio Silveira, Marcos Antônio Almeida Santos, Antônio Carlos Sobral Sousa, Jussiely Cunha Oliveira
Journal: Journal of the American College of Cardiology (2017)