tbuckley/cabot-search huggingface dataset:
Tissue-Type Plasminogen Activator in Breast Cancer: Relationship With Estradiol and Progesterone Receptors
Authors: M. J. Duffy, P. O'Grady, J. Simon, M. Rose, H. R. Lijnen
Journal: JNCI Journal of the National Cancer Institute (1986)

Plasminogen activator (PA) is an estradiol-inducible enzyme and therefore a potential marker for a functional estradiol receptor (ER) in human breast carcinomas. In this investigation tissue-type PA (t-PA) correlated significantly with both ER and progesterone receptors (PR) in human breast carcinomas. In contrast, neither total PA activity nor urokinase-like PA showed any significant correlation with either ER or PR. Other proteases such as a trypsin-like protease, a chymotrypsin-like protease, and cathepsin B also showed no correlation with ER and PR. It was concluded that the t-PA form of PA may be a marker for a functional ER in breast carcinoma and thus be of value in predicting hormone-dependent breast cancers.
Validation of BARC Bleeding Criteria in Patients With Acute Coronary Syndromes
Authors: Pascal Vranckx, Harvey D. White, Zhen Huang, Kenneth W. Mahaffey, Paul W. Armstrong, Frans Van de Werf, David J. Moliterno, Lars Wallentin, Claes Held, Philip E. Aylward, Jan H. Cornel, Christoph Bode, Kurt Huber, José C. Nicolau, Witold Ruzyllo, Robert A. Harrington, Pierluigi Tricoci
Journal: Journal of the American College of Cardiology (2016)

The Bleeding Academic Research Consortium (BARC) scale has been proposed to standardize bleeding endpoint definitions and reporting in cardiovascular trials. Validation in large cohorts of patients is needed. This study sought to investigate the relationship between BARC-classified bleeding and mortality and compared its prognostic value against 2 validated bleeding scales: TIMI (Thrombolysis In Myocardial Infarction) and GUSTO (Global Use of Strategies to Open Occluded Arteries). We analyzed bleeding in 12,944 patients with acute coronary syndromes without ST-segment elevation, with or without early invasive strategy. The main outcome measure was all-cause death. During follow-up (median: 502 days), noncoronary artery bypass graft (CABG) bleeding occurred in 1,998 (15.4%) patients according to BARC (grades 2, 3, or 5), 484 (3.7%) patients according to TIMI minor/major, and 514 (4.0%) patients according to GUSTO moderate/severe criteria. CABG-related bleeding (BARC 4) occurred in 155 (1.2%) patients. Patients with BARC (2, 3, or 4) bleeding had a significant increase in risk of death versus patients without bleeding (BARC 0 or 1); the hazard was highest in the 30 days after bleeding (hazard ratio: 7.35; 95% confidence interval: 5.59 to 9.68; p < 0.0001) and remained significant up to 1 year. The hazard of mortality increased progressively with non-CABG BARC grades. BARC 4 bleeds were significantly associated with mortality within 30 days (hazard ratio: 10.05; 95% confidence interval: 5.41 to 18.69; p < 0.0001), but not thereafter. Inclusion of BARC (2, 3, or 4) bleeding in the 1-year mortality model with baseline characteristics improved it to an extent comparable to TIMI minor/major and GUSTO moderate/severe bleeding. In patients with acute coronary syndromes without ST-segment elevation, bleeding assessed with the BARC scale was significantly associated with risk of subsequent death up to 1 year after the event and risk of mortality increased gradually with higher BARC grades. Our results support adoption of the BARC bleeding scale in ACS clinical trials. (Trial to Assess the Effects of Vorapaxar [SCH 530348; MK-5348] in Preventing Heart Attack and Stroke in Participants With Acute Coronary Syndrome [TRACER] [Study P04736]; NCT00527943)
Final results from study 181: Randomized phase III study of FOLFIRI with or without panitumumab (pmab) for the treatment of second-line metastatic colorectal cancer (mCRC).
Authors: Alberto F. Sobrero, Marc Peeters, Timothy Jay Price, Yevhen Hotko, Andres Cervantes-Ruiperez, Michel Ducreux, Thierry Andre, Emily Chan, Florian Lordick, Ying Tian, Roger Sidhu
Journal: Journal of Clinical Oncology (2012)

387 Background: In the primary analysis of study 181, pmab+FOLFIRI significantly improved progression-free survival (PFS) vs FOLFIRI as second-line therapy in patients (pts) with wild-type (WT) KRAS mCRC. Here, we report the results of a prespecified final descriptive analysis planned for 30 months (mos) after the last pt was enrolled. Methods: Pts were randomised 1:1 to pmab 6.0 mg/kg Q2W+FOLFIRI (Arm 1) vs FOLFIRI alone (Arm 2). Pts had one prior fluoropyrimidine-based chemotherapy regimen for mCRC and ECOG 0-2. The co-primary endpoints were PFS (central assessment) and OS, and were independently tested. Secondary endpoints included objective response rate (ORR), and safety. KRAS status was determined by a blinded central lab. Results: 1,186 pts were randomised and received treatment (tx): 591 in Arm 1, 595 In Arm 2. 1,083/1,186 pts (91%) had KRAS results. Adverse event rates were consistent with the primary analysis. Results are shown in the table . Conclusions: In Arm 1, PFS (standard and on-treatment definition) and ORR were improved, and there was a trend toward improved OS in pts with WT KRAS mCRC. The large proportion of pts receiving post-progression anti-EGFR therapy may have affected the ability to observe a difference in OS between the tx arms. In pts with MT KRAS there was no difference in efficacy. KRAS testing is critical to select appropriate pts for tx with pmab. [Table: see text]
Current Understanding on Role of the Wnt Signaling Pathway Effector TCF7L2 in Glucose Homeostasis
Authors: Tianru Jin
Journal: Endocrine Reviews (2016)

The role of the Wnt signaling pathway in metabolic homeostasis has drawn our intensive attention, especially after the genome-wide association study discovery that certain polymorphisms of its key effector TCF7L2 are strongly associated with the susceptibility to type 2 diabetes. For a decade, great efforts have been made in determining the function of TCF7L2 in various metabolic organs, which have generated both considerable achievements and disputes. In this review, I will briefly introduce the canonical Wnt signaling pathway, focusing on its effector β-catenin/TCF, including emphasizing the bidirectional feature of TCFs and β-catenin post-translational modifications. I will then summarize the observations on the association between TCF7L2 polymorphisms and type 2 diabetes risk. The main content, however, is on the intensive functional exploration of the metabolic role of TCF7L2, including the disputes generated on determining its role in the pancreas and liver with various transgenic mouse lines. Finally, I will discuss those achievements and disputes and present my future perspectives.
Soundings: Holes in the heart
Authors: George Dunea
Journal: BMJ (2002)

Every Saturday our local newspapers publish a column on “What happened on your favourite soaps,” which includes the week's most exciting medical events. A sample might read as follows: Keisha and David put aside their differences to save Eve, who was found to have a hole in her heart and possibly a lethal virus. Miranda, who occupied the next bed, fled from the hospital in the middle of the night. Brandon used Reva's blood for DNA testing and was stunned when the test came up an exact match of Brenda's daughter. Dr Jones was caught between his professional duties and personal friendships. Rhonda was a perfect match for Amber, but her liver was too damaged from alcoholism. Daron wed Roseanne, but shortly after the marriage ceremony went into cardiac arrest and was found to have two holes in his heart. Coming: Reva makes a mysterious call.

Alex became suspicious of Charlie when he implied that Barbara's DNA would never match Marvin's. A homeless Brenda, determined to murder David, stole a poisonous vial and headed for the office. When the police discovered bloodstains in the receptionist's office, Maria jumped out of the window. Unable to remember what she did with the vial, Brenda fainted during the interrogation. Miranda unexpectedly reappeared, but now the police discovered that Suzie's burial site had been disturbed. Felicia collapsed and was found to have three holes in her heart.

When the body was exhumed, Reva feared that Dr Jones's secret might be uncovered. Daron received a heart transplant and immediately asked for a divorce. When lightning struck, Rhonda disintegrated into a pile of ash, and Keisha experienced sharp abdominal pains. Coming: Brandon suffers from vampire-like symptoms; Dr Jones makes a surprising confession.

Daron was told that the heart came from Arianna, and Angel tried to seduce Keisha. Sweeney, the drug dealer, was found strangled in his car. Ben held the key to the cure that could save Belinda's life. Shocked about the results of the HIV test, Isaac threatened to kill Brandon. Eve finally managed to move her foot, refusing to accept that she would never walk again. Starr obtained a love potion and put it in Reva's lemonade. Miranda was filled with sudden strength after receiving a blood transfusion and again bolted out of the hospital. Coming: Suzie reappears and Dr Jones has four holes in his heart (and one in his head).
Clinicopathological characteristics of subsequent breast cancers in patients with benign breast disease
Authors: R. Santana-Davila, D. W. Visscher, C. M. Vachon, M. Frost, R. A. Vierkant, S. S. Anderson, A. C. Degnim, L. C. Hartmann
Journal: Journal of Clinical Oncology (2009)

1061 Background: Benign breast disease (BBD) is a significant risk factor for breast cancer (BC); however little is known about the aggressiveness of the BCs these patients develop. Shared features between select atypias and low-grade DCIS have led some to speculate that a history of BBD portends the development of well-differentiated BCs. Methods: The Mayo BBD cohort includes 9,376 women who had benign breast biopsies from 1967–1991. Data on BC events were obtained from medical records and questionnaires. Tissue from the BCs was reviewed by a single breast pathologist (DWV). Results: Our cohort included 6,244 patients with nonproliferative disease (NP), 2,801 women with proliferative disease without atypia (PDWA), and 331 with atypical hyperplasias (AH). With a median of 18 years of follow-up, 799 patients with BBD have developed breast cancer, 416 initially had NP, 313 had PDWA, and 70 AH. BC tissue was available for 703 of the women. The cancers were invasive ductal in 76.1% (n = 535), invasive lobular in 9.4% (n = 66), and DCIS alone in 14.5% (n = 102) patients. Grade is currently available for 500 women, and is well differentiated in 29.4% (n = 150), moderately differentiated in 42.7% (n = 218) and poorly differentiated in 27.8% (n = 142). In 537 cases the malignant tissue had a concurrent benign component consisting of NP in 24% (n = 129), PDWA in 25.1% (n = 135), and AH in 50.8% (n = 273). In regards to tumor size, 69.6% had T1 tumors, 24.9% T2 tumors, and 5.5% T3 disease. Metastasis to lymph nodes occurred in 25% of patients. Median time to BC was 12.3 years and did not differ across the different benign entities. Breast cancer developed within 5 years from the initial BBD in 163 women (20%). In this group, tumor size was greater (p = 0.02), and there were more poorly differentiated tumors (p = 0.006) than in those who later developed BC. Conclusions: In the BCs that have developed in our BBD cohort, we do not see a preponderance of well-differentiated, good-risk BCs. Patients diagnosed within 5 years of BBD appear to have BCs with more aggressive features. No significant financial relationships to disclose.
Chromosome Studies in Human Leukemia. II. Chronic Granulocytic Leukemia
Authors: Nowell, Peter C., Hungerford, David A.
Journal: JNCI Journal of the National Cancer Institute (1961)

Chromosome Studies in Human Leukemia. II. Chronic Granulocytic Leukemia Get access Peter C. Nowell, Peter C. Nowell Department of Pathology, School of Medicine, University of Pennsylvania, and The Institute for Cancer Research, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar David A. Hungerford David A. Hungerford Department of Pathology, School of Medicine, University of Pennsylvania, and The Institute for Cancer Research, Philadelphia, Pennsylvania Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 27, Issue 5, November 1961, Pages 1013–1035, https://doi.org/10.1093/jnci/27.5.1013 Published: 01 November 1961 Article history Received: 27 June 1961 Published: 01 November 1961
Eosinophil Mediators in Nasal Washes Obtained during Experimental Infections with Rhinovirus-16 in Subjects with and without Asthma
Authors: Evan Rajadhyaksha, Patricia P. Jorge, Holliday T. Carper, Deborah D. Murphy, Lisa J. Workman, Thomas A.E. Platts-Mills, Kate Donowitz, Peter W. Heymann
Journal: Journal of Allergy and Clinical Immunology (2016)
Phase 3 Trial of Brentuximab Vedotin and Chp Versus Chop in the Frontline Treatment of Patients (Pts) with Cd30+ Mature T-Cell Lymphomas (Mtcl)
Authors: T. Illidge, B. Pro, L.H. Trümper, E.K. Larsen, D. Huebner, D.A. Kennedy, O. O'Connor
Journal: Annals of Oncology (2014)
TEL-JAK2 constitutively activates the extracellular signal-regulated kinase (ERK), stress-activated protein/Jun kinase (SAPK/JNK), and p38 signaling pathways.
Authors: Jenny M.-Y. Ho, Melody H.-H. Nguyen, Jamil K. Dierov, Karla M. Badger, Bryan K. Beattie, Piero Tartaro, Rizwan Haq, Brent W. Zanke, Martin P. Carroll, Dwayne L. Barber
Journal: Blood (2002)
P0846 : Evaluation of adherence to telaprevir (TVR) and boceprevir (BOC) using different thresholds
Authors: E. González-Colominas, T. Broquetas, A. Retamero, M. García-Retortillo, N. Cañete, M. Puigvehí, R. Pellicer, D. Giménez, B. Cabrero, F. Bory, E. Salas, R. Solà, J.A. Carrión
Journal: Journal of Hepatology (2015)
BMA loses challenge to “unfair” GMC rule
Authors: Clare Dyer
Journal: BMJ (2016)

The BMA has lost its challenge in the High Court to a new General Medical Council rule for fitness to practise tribunals that the doctors’ union had branded unfair and “irrational.”

The rule that legally qualified chairs could give advice to other tribunal members during their private deliberations without disclosing it to the doctor facing misconduct allegations breached the right to a fair hearing, the BMA argued at the High Court in London.

The new rule was adopted in December 2015 after the GMC decided to use lawyers to chair tribunals in some cases, doing away with the need for a legal assessor in those cases. Unless the …
Human teaching and learning involve cultural communities, not just individuals
Authors: Barbara Rogoff
Journal: Behavioral and Brain Sciences (2015)

Cultural accounts of how people facilitate learning extend beyond the five types of teaching outlined by Kline's target article. Rather than focusing so exclusively on individual teaching, cultural accounts examine the mutually constituting efforts of individuals who are teaching, together with those who are learning. Further, cultural research emphasizes the community contexts of people's arrangements for learning and their teaching/learning interactions.
Following a Trial That Stopped Early: What Next for Adjuvant Hepatic Intra-Arterial Iodine-131 Lipiodol in Resectable Hepatocellular Carcinoma?
Authors: S. B. Tan, D. Machin, Y. B. Cheung, Y. F.A. Chung, B. C. Tai, D. Machin
Journal: Journal of Clinical Oncology (2002)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.6.1709 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11896125 Following a Trial That Stopped Early: What Next for Adjuvant Hepatic Intra-Arterial Iodine-131 Lipiodol in Resectable Hepatocellular Carcinoma? S. B. TanxS. B. TanSearch for articles by this author , D. MachinxD. MachinSearch for articles by this author , Y. B. CheungxY. B. CheungSearch for articles by this author , Y. F.A. ChungxY. F.A. ChungSearch for articles by this author , B. C. TaixB. C. TaiSearch for articles by this author , D. MachinxD. MachinSearch for articles by this author Show More National Cancer Centre, SingaporeSingapore General Hospital, SingaporeNational Medical Research Council, SingaporeUniversity of Sheffield, Sheffield, United Kingdom https://doi.org/10.1200/JCO.2002.20.6.1709 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
Association between Preoperative Vascular Function and Postoperative Arteriovenous Fistula Development
Authors: Michael Allon, Tom Greene, Laura M. Dember, Joseph A. Vita, Alfred K. Cheung, Naomi M. Hamburg, Peter B. Imrey, James S. Kaufman, Michelle L. Robbin, Yan-Ting Shiu, Christi M. Terry, Heidi R. Umphrey, Harold I. Feldman
Journal: Journal of the American Society of Nephrology (2016)

Arteriovenous fistula (AVF) maturation failure is the primary cause of dialysis vascular access dysfunction. To evaluate whether preoperative vascular functional properties predict postoperative AVF measurements, patients enrolled in the Hemodialysis Fistula Maturation Study underwent up to five preoperative vascular function tests (VFTs): flow-mediated dilation (FMD), nitroglycerin-mediated dilation (NMD), carotid-femoral pulse wave velocity, carotid-radial pulse wave velocity, and venous occlusion plethysmography. We used mixed effects multiple regression analyses to relate each preoperative VFT to ultrasound measurements of AVF blood flow rate and venous diameter at 1 day, 2 weeks, and 6 weeks after AVF placement. After controlling for AVF location, preoperative ultrasound measurements, and demographic factors (age, sex, race, and dialysis status), greater NMD associated with greater 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in NMD: change in blood flow rate =14.0%; 95% confidence interval [95% CI], 3.7% to 25.3%; P &lt;0.01; change in diameter =0.45 mm; 95% CI, 0.25 to 0.65 mm; P &lt;0.001). Greater FMD also associated with greater increases in 6-week AVF blood flow rate and AVF diameter (per absolute 10% difference in FMD: change in blood flow rate =11.6%; 95% CI, 0.6% to 23.9%; P =0.04; change in diameter =0.31 mm; 95% CI, 0.05 to 0.57 mm; P =0.02). None of the remaining VFT parameters exhibited consistent statistically significant relationships with both postoperative AVF blood flow rate and diameter. In conclusion, preoperative NMD and FMD positively associated with changes in 6-week AVF blood flow rate and diameter, suggesting that native functional arterial properties affect AVF development.
Relationship between patterns of engraftment in peripheral blood and immune reconstitution after allogeneic bone marrow transplantation for (severe) combined immunodeficiency
Authors: JE van Leeuwen, MJ van Tol, AM Joosten, PT Schellekens, RL van den Bergh, JL Waaijer, NJ Oudeman-Gruber, CP van der Weijden-Ragas, MT Roos, EJ Gerritsen
Journal: Blood (1994)
Subdermal Flexible Solar Cell Arrays for Powering Medical Electronic Implants
Authors: Kwangsun Song, Jung Hyun Han, Taehoon Lim, Namyun Kim, Sungho Shin, Juho Kim, Hyuck Choo, Sungho Jeong, Yong‐Chul Kim, Zhong Lin Wang, Jongho Lee
Journal: Advanced Healthcare Materials (2016)

A subdermally implantable flexible photovoltatic (IPV) device is proposed for supplying sustainable electric power to in vivo medical implants. Electric properties of the implanted IPV device are characterized in live animal models. Feasibility of this strategy is demonstrated by operating a flexible pacemaker with the subdermal IPV device which generates DC electric power of ≈647 μW under the skin. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Epigenetic changes mediated by polycomb repressive complex 2 and E2a are associated with drug resistance in a mouse model of lymphoma
Authors: Colin Flinders, Larry Lam, Liudmilla Rubbi, Roberto Ferrari, Sorel Fitz-Gibbon, Pao-Yang Chen, Michael Thompson, Heather Christofk, David B Agus, Daniel Ruderman, Parag Mallick, Matteo Pellegrini
Journal: Genome Medicine (2016)

The genetic origins of chemotherapy resistance are well established; however, the role of epigenetics in drug resistance is less well understood. To investigate mechanisms of drug resistance, we performed systematic genetic, epigenetic, and transcriptomic analyses of an alkylating agent-sensitive murine lymphoma cell line and a series of resistant lines derived by drug dose escalation. Dose escalation of the alkylating agent mafosfamide was used to create a series of increasingly drug-resistant mouse Burkitt's lymphoma cell lines. Whole genome sequencing, DNA microarrays, reduced representation bisulfite sequencing, and chromatin immunoprecipitation sequencing were used to identify alterations in DNA sequence, mRNA expression, CpG methylation, and H3K27me3 occupancy, respectively, that were associated with increased resistance. Our data suggest that acquired resistance cannot be explained by genetic alterations. Based on integration of transcriptional profiles with transcription factor binding data, we hypothesize that resistance is driven by epigenetic plasticity. We observed that the resistant cells had H3K27me3 and DNA methylation profiles distinct from those of the parental lines. Moreover, we observed DNA methylation changes in the promoters of genes regulated by E2a and members of the polycomb repressor complex 2 (PRC2) and differentially expressed genes were enriched for targets of E2a. The integrative analysis considering H3K27me3 further supported a role for PRC2 in mediating resistance. By integrating our results with data from the Immunological Genome Project (Immgen.org), we showed that these transcriptional changes track the B-cell maturation axis. Our data suggest a novel mechanism of drug resistance in which E2a and PRC2 drive changes in the B-cell epigenome; these alterations attenuate alkylating agent treatment-induced apoptosis.
The value of studying cancer families.
Authors: J E Garber, F P Li
Journal: Journal of Clinical Oncology (1990)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1990.8.4.574 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2313327 The value of studying cancer families. J E GarberxJ E GarberSearch for articles by this author , F P LixF P LiSearch for articles by this author https://doi.org/10.1200/JCO.1990.8.4.574 PDF "The value of studying cancer families.." Journal of Clinical Oncology, 8(4), pp. 574–575© 1990 by American Society of Clinical Oncology