tbuckley/cabot-search huggingface dataset:
Abstract P6-09-47: The development of personalized diagnostic tests and therapeutic strategies in breast cancer
Authors: JR Kutasovic, E Rozali, M Miranda, SR Lakhani, F Al-Ejeh
Journal: Cancer Research (2017)

Abstract Despite some improvement in the overall survival rates of breast cancer, it remains as a leading cause of cancer-related deaths in women. Currently, we are unable to accurately predict patients' response to therapies and their long-term outcome. We developed and patented a 275-gene signature based on in silico meta-analysis of global transcriptome profiles (approximately 10,000 cases) that can predict which patients suffer from aggressive disease and succumb to their disease within 5 years of diagnosis. This test, the integrated Breast Cancer Recurrence (iBCR) score outperformed every clinicopathological indicator available in three independent, large cohorts of breast cancer. The iBCR can also predict the likelihood of response to standard treatments and which emerging targeted therapies should be added to an individual's treatment regime to improve outcomes. In addition, 21 of the genes in this signature are novel potential drug targets that have not previously been described in aggressive breast tumours. We performed a pilot study using the NanoString nCounter Dx platform to measure the expression of the top 125 genes within the signature in a cohort of 48 patients. We have validated with 100% accuracy the prognostic power of the iBCR in the Queensland Follow Up (QFU) cohort with 25 years of follow up (p&amp;lt;0.0001), irrespective of clinicopathological features. Our pilot study using the Nanostring platform successfully counted mRNA molecules from samples that averaged 26.8 years of age (range 24 – 29 years), with an average RNA Integrity (RIN) score of 2.4. Future work will expand this test to the full 275-gene set across 500 patients from the QFU cohort. In vitro siRNA screening of the 21 novel genes revealed that at least 10 of these genes are required for breast cancer cell survival. We have started validation of the top 4 hits and these studies confirm the requirement of these genes in breast cancer progression. These data will pave the way towards the study of these genes as new drug targets. Collectively, our test addresses the significant issue of heterogeneous responses to breast cancer treatment. The iBCR platform aims to improve both patients' clinical outcome and quality of life by directing more appropriate treatment with greater likelihood of success, and preventing overtreatment for those with a less aggressive tumor type. Citation Format: Kutasovic JR, Rozali E, Miranda M, Lakhani SR, Al-Ejeh F. The development of personalized diagnostic tests and therapeutic strategies in breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-47.
Cardiovascular Events Among Patients with Chronic Myeloid Leukemia (CML) Treated with Tyrosine Kinase Inhibitors (TKIs)
Authors: Princy Yohannan Sam, Hycienth Ahaneku, Graciela M. Nogueras-Gonzalez, Elias Jabbour, Guillermo Garcia-Manero, Gautam Borthakur, William G. Wierda, Naval Daver, Tapan Kadia, Jan Burger, Sherry Pierce, Courtney D DiNardo, Farhad Ravandi, Hagop M. Kantarjian, Jorge E. Cortes
Journal: Blood (2016)
Features of Avascular Osteonecrosis in Children Treated for Acute Lymphoblastic Leukaemia: Experience in a Single Center
Authors: Giada Biddeci, Elena Varotto, Maria Paola Boaro, Stefania Varotto, Antonio Marzollo, Maria Gabelli, Roya Assadi, Giacomo Garetto, Cosimo Gigante, Giuseppe Basso, Maria Caterina Putti
Journal: Blood (2016)
Comparing the Outcome of Diffuse Large B-Cell Lymphoma in Very Elderly Patients (age greater than 80 years) with Elderly Patients (age between 65 to 79 years)
Authors: Charalampos S. Floudas, Ajay Dhakal, Sunjay Neupane, Pouyan Gohari, Abhinav B Chandra
Journal: Blood (2015)
Imatinib (IM) and Interferon-Alpha (IFN-a) Maintenance Therapy Is Associated with Long-Term DFS in a Subset of Elderly Patients with Philadelphia-Positive Acute Lymphoblastic Leukemia (Ph+ALL)
Authors: Heike Pfeifer, Sylvia Wystub, A. Binckebanck, Barbara Wassmann, Andreas Käbisch, Michael Lübbert, Lothar Leimer, Aristoteles Giagounidis, Winfried Gassmann, Patrick Brueck, Hubert Serve, Dieter Hoelzer, Oliver G. Ottmann
Journal: Blood (2012)
Modelling Resistance to Emerging Epigenetic Therapies
Authors: Chun Yew Fong, Omer Gilan, Enid Lam, Alan Rubin, Jessica Morison, George Giotopoulos, Kym Stanley, Ftouni Sarah, Dean Tyler, Dave Lugo, Philip Jeffrey, Richard Gregory, Jaring Schreuder, Shalin Naik, Tony Kouzarides, Brian Huntly, Ricky W Johnstone, Rab K Prinjha, Anthony Papenfuss, Mark A Dawson
Journal: Blood (2014)
Substance Use Terminology
Authors: Katherine E. Calver, Richard Saitz
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Abstract 14529: Long Term Prognosis Using Plaque Characteristics by Coronary Computed Tomography Angiography: A 9-Year Follow-Up of 3255 Patients
Authors: Sadako Motoyama, Masayoshi Sarai, Hideki Kawai, Hajime Ito, Shino Kan, Hiroyuki Naruse, Junichi Ishii, Yukio Ozaki
Journal: Circulation (2012)

Purpose: Coronary computed tomography angiography (CCTA) has a potential to predict acute coronary syndrome (ACS) with plaque characteristics of high risk plaque (HRP; positive remodeling and/or lo...
Acetylated tubulin and risk of nodal metastases in squamous cell carcinoma of the head and neck (SCCHN).
Authors: Nabil F. Saba, Kelly R. Magliocca, Sungjin Kim, Susan Muller, Zhengjia Chen, Carrie Eggers, Vanessa H Phelan, Scott A. Kono, Taofeek Kunle Owonikoko, Suresh S Ramalingam, William Grist, Amy Y. Chen, Jonathan Jay Beitler, Dong M Shin, Adam Marcus, Fadlo Raja Khuri
Journal: Journal of Clinical Oncology (2012)

5560 Background: We previously established that AT expression predicts for response to chemotherapy in SCCHN (Saba et al, AACR 2010 meeting abstr 3744). We wanted to further examine the relation of AT expression and nodal metastases in SCCHN. Methods: We assessed AT expression in archival tissue specimens from primary SCCHN cases with (50 cases) and without (53 cases) lymph node metastases (NM) using standard immunohistochemistry (IHC). Clinical characteristics of patients were retrieved from the department of pathology under the guidelines of the institutional review board (IRB). IHC staining for AT was scored based on intensity and percentage of tumor cells stained: 0 = no staining, 1+ = weak, 2+ = moderate, 3+ = moderate to high, 4+ = high and a weighted index (WI) was calculated as percent stain x stain intensity. Wilcoxon two-sample test and Kruskal-Wallis test were used to estimate the relationships of the WI with nodal metastasis, node status, primary tumor location, grade, and stage. Log-rank test was used to examine the difference in OS and DFS among four groups based on quartiles of the WI. A Cox proportional hazard model was employed to estimate the adjusted effect of WI on OS and DFS. Results: A higher AT expression was associated with nodal metastasis (p=0.0155) and higher stage (p=0.0311). A lower AT expression was associated with oral cavity primary (p=0.0107). After adjusting for age, gender, race, and smoking status, a lower AT expression was significantly associated with better DFS in the subset of patients with NM by multivariate analysis (HR=1.008; 95% CI=1.002- 1.014; p=0.0123). Among patients with no NM there was a marginally significant difference in OS among four different groups based on quartiles of AT expression (p=0.0765). Conclusions: High AT expression is associated with nodal metastases in SCCHN and may be a marker of poor prognosis in patients with node positive disease. The value of AT as a prognostic marker in SCCHN needs to be better defined. This work is supported by a SPORE CDP Grant P50 CA128613-03 to NFS.
Lower Doses of Plerixafor Use Is Sufficient to Effectively Mobilize PBSC (Peripheral Blood Hematopoetic Stem Cells) When Compared to Standard Administration
Authors: Hakan Goker, Eylem Eliacik, Fevzi Altuntas, Emre Tekgunduz, Evren Ozdemir, Ayse Isik, Omur Kayikci, Ali Hakan Kaya, Salih Aksu, Ibrahim C. Haznedaroglu, Nilgun Sayinalp, Haluk Demiroglu, Osman Ilhami Ozcebe, Yahya Buyukasik
Journal: Blood (2014)
Plasma biomarkers to predict or rule out early post‐discharge events after hospitalization for acute heart failure
Authors: Biniyam G. Demissei, Douwe Postmus, John G. Cleland, Christopher M. O'Connor, Marco Metra, Piotr Ponikowski, John R. Teerlink, Gad Cotter, Beth A. Davison, Michael M. Givertz, Daniel M. Bloomfield, Dirk J. van Veldhuisen, Howard C. Dittrich, Hans L. Hillege, Adriaan A. Voors
Journal: European Journal of Heart Failure (2017)
Government must plan for next winter now, says NHS Providers
Authors: Anne Gulland
Journal: BMJ (2017)

The body that represents NHS service providers is calling on the government to start planning for next winter now, after an analysis it did of NHS performance over the past three months showed that hospitals are struggling to cope.

NHS Providers analysed the performance of 152 trusts in England between December 2016 and February 2017 in a range of measures, including emergency department attendances and diverts to other hospitals, emergency admissions, and bed occupancy rates.1

The analysis showed that in the week beginning Monday 30 January an extra 32 558 beds were opened to provide more capacity, up from 20 760 additional beds opened in the week beginning 5 December. That figure dropped over the following weeks and in the week beginning 20 February stood at 26 762 extra beds.

NHS Providers said that because the average hospital …
Salvage Therapy with Vorinostat, Lenalidomide, and Dexamethasone (ZRD) in Lenalidomide/Dexamethasone Relapsed/Refractory Multiple Myeloma,
Authors: Joshua R. Richter, Elizabeth Bilotti, Laura McBride, Linda Schmidt, Zhijie Gao, Madiha Tufail, Palka Anand, Ann McNeill, Urszula Bednarz, Thorsten Graef, David H. Vesole, David S. Siegel
Journal: Blood (2011)
Marit Westerterp
Authors: Ruth Williams
Journal: Circulation Research (2017)

Marit Westerterp's research has been focused on atherosclerosis and the molecular mechanisms of cholesterol efflux and transport 1-5 -a subject she will continue to pursue in her upcoming role as associate professor at the University of Groningen in the Netherlands.Circulation Research caught up with Westerterp during her busy transition period and discovered that although this young researcher is a little reserved when talking about her personal life, she is forthcoming and enlightening on the subjects of research and career.In fact, she stresses how important conversations with colleagues are for success in one's scientific life.Communicating with fellow scientists, Westerterp says, has helped her to cope with tough times, to find new career opportunities, and to expand her research in new directions.And she now fosters such communications and exchanges of ideas in others through her work for the Netherland America Foundation, which promotes cultural and student exchanges between the 2 countries.In her conversation with Circulation Research, Westerterp did share a few personal details.For instance, she spoke of growing up in the Netherlands, of being a keen violinist, and of the fact that both her mother and father are themselves research biologists.
Cardiac Iron Loading Measured by Multislice Multiecho T2* MRI and Cardiac Disease In Male and Female Patients with Thalassemia Major
Authors: Alessia Pepe, Maria Marsella, Antonella Meloni, Valeria Caldarelli, Maria Chiara Dell'Amico, Elisabetta Chiodi, Gianluca Valeri, Vincenzo Positano, Lucia De Franceschi, Massimo Lombardi, Caterina Borgna-Pignatti
Journal: Blood (2010)
Diferric Transferrin-Sensed Hepcidin Upregulation in Human Hepatoma-Derived Cell Line Is Differentially Controlled in Each Isoform 20, 22, 25; Confirmation by a Novel Simultaneous Quantification by Liquid Chromatography/ Tandem Mass Spectrometry.
Authors: Katsuya Ikuta, Takaaki Hosoki, Yasushi Shimonaka, Yusuke Sasaki, Hideyuki Yasuno, Takaaki Ohtake, Katsunori Sasaki, Yoshihiro Torimoto, Keiji Saito, Yutaka Kohgo
Journal: Blood (2009)
Oligometastatic non-small cell lung cancer treated with curative intent.
Authors: Jamie Y. Hung, Humdum Pasha Durrani, Raid Aljumaily, Hyder Husain Arastu, Clinton Leinweber, Julian Rosenman, Paul R. Walker
Journal: Journal of Clinical Oncology (2014)

e19034 Background: Stage IV non-small cell lung cancer (NSCLC) carries a poor prognosis with a median survivals of 8-10 months (up to 16-19 months with maintenance therapy in adenocarcinoma) and 3 year survivals of less than 10%. The standard of care has traditionally been palliative chemotherapy and radiation (typically 30Gy) for symptom relief. Some data has suggested that patients with solitary or oligometastatic NSCLC (OM-NSCLC) can be cured if the known sites of metastatic disease are eradicated and the primary tumor treated in a curative fashion. In our institution, we have adopted such a treatment approach for OM-NSCLC patients; we aim for a curative potential with ablative treatment to the metastatic sites and definitive treatment to the primary disease. Methods: From our institutional thoracic oncology database, we identified and analyzed data from patients with OM-NSCLC treated with curative intent from 2006 to 2012. Curative intent treatment was defined as definitive treatment (>55 Gy of radiation concurrent with chemotherapy or surgery) of the primary and local ablative therapy to the known metastatic sites, either surgery, stereotactic radiosurgery or high dose external beam therapy. Overall survivals (OS) were calculated using the Life Table method. Results: 53 patients (29 men and 24 women) with a median of one treated oligometastatic lesion (range 1 to > 5) were identified and reviewed. Median age was 60 years (41-79 years). Overall median and 3-year survival were 17 months and 17%, respectively. Median OS of the 28 patients with adenocarcinoma was 25 months. Median OS of the 25 patients with non-adenocarcinoma was significantly lower at 14 months (p=0.01). The 3-year OS of patients with adenocarcinoma was 30% and non-adenocarcinoma was 0%. The survival curve of those with intrathoracic stage IIIA plateaued, suggesting a cure potential even in mediastinal node positive disease. Over 90% of the patients received second-line chemotherapies upon progression of disease. Conclusions: Our results indicate that curative intent treatment of OM-NSCLC can achieve prolonged median survival and 3-year survival potential in adenocarcinoma. Survival benefits in these patients also exceed what has been achieved with maintenance chemotherapy.
Abstract MP009: Contemporary Risk Stratification After Myocardial Infarction in the Community: Performance of Scores and Incremental Value of ST2
Authors: Yariv Gerber, Susan Weston, Maurice Enriquez-Sarano, Allan Jaffe, Sheila Manemann, Ruoxiang Jiang, Veronique L Roger
Journal: Circulation (2017)

Background: Current AHA/ACC guidelines recommend the GRACE and TIMI scores for assessing myocardial infarction (MI) prognosis. With recent major changes in the epidemiology of MI and new biomarkers available for risk stratification, an updated assessment of the performance of these scores is needed in a real-world practice setting. Objectives: We assessed (a) the performance of GRACE and TIMI in predicting 1-year mortality among a community cohort of MI patients stratified by ST- and non-ST-segment elevation MI (STEMI/NSTEMI) and (b) the incremental discriminatory power of soluble ST2, a myocardial fibrosis biomarker. Methods: Olmsted County, Minnesota residents with incident MI (N=1,401) were recruited prospectively from 2002-2012 (mean age, 67 years; 61% men; 79% NSTEMI). Baseline data were used for calculating risk scores; stored plasma samples obtained shortly after MI were used for ST2 measurement. C -statistics adapted to survival data were used to assess the discriminatory power of GRACE and TIMI and the improvement gained by incorporating additional variables. Results: During the first year of follow-up, 190 (14%) patients died. The overall discriminatory performance in predicting death was reasonable for GRACE and poor for TIMI, and was generally worse in NSTEMI vs STEMI. In NSTEMI, sequential addition of comorbidities and ST2 substantially improved the c -statistic over GRACE (from 0.78 to 0.80 to 0.84) and TIMI (from 0.61 to 0.73 to 0.81), respectively (all P ≤ 0.05). Conclusions: Guidelines-recommended scores for risk assessment post-MI underperform in contemporary community patients with NSTEMI, which now represent the majority of infarcts. Incorporating comorbidities and ST2 substantially improves risk prediction thereby delineating opportunity to improve clinical care.
Abstract IA03: Lessons from colorectal cancer
Authors: Kenneth W. Kinzler
Journal: Cancer Research (2017)

Abstract Many of the fundamental tenets of cancer genetics have their origins in the study of colorectal cancer (CRC). This is, at least in part, due to several clinical features of CRC that make it a particularly attractive and amenable to study in humans. Some of these key features include the relative abundance of CRC and precursor adenomas in the general population, the ease of identifying and collecting adenomas through routine screening colonoscopies, the existence of well recognized histopathological classifications with defined clinical implications and the long standing description of several well defined inherited predispositions. As a result, studies in CRC have often proven to be seminal in defining the role of somatic mutations and germline variations in the initiation progression and resistance of human cancer. Moreover, studies of CRC have proven to be influential beyond the aforementioned areas helping to define the roles of diet, inflammation and the microbiome in human cancer and providing new paradigms for the prevention and management of cancer. How these findings inform our understanding of CRC and cancer in general will be discussed with special emphasis on emerging topics highlighted in this conference. Citation Format: Kenneth W. Kinzler. Lessons from colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer: From Initiation to Outcomes; 2016 Sep 17-20; Tampa, FL. Philadelphia (PA): AACR; Cancer Res 2017;77(3 Suppl):Abstract nr IA03.
PP03. HUMAN ENDOGENOUS RETROVIRUS TYPE K (HERVK) PROTEINS ARE OVEREXPRESSED AND RELEASED FROM HUMAN PRIMARY SCHWANNOMA CELLS CONTRIBUTING TO TUMOUR DEVELOPMENT VIA ERK, AKT, FAK PATHWAYS ACTIVATION AND P53 DOWNREGULATION
Authors: Dr Sylwia Ammoun, Mr Emmanuel Maze, Ms Shona Reeves, Dr David Hilton, Dr Emanuela Ercolano, Prof Oliver Hamemann, Dr Robert Belshaw
Journal: Neuro-Oncology (2017)

Loss of function mutations in the gene coding for the tumour suppressor Merlin causes development of multiple tumours of the nervous system such as schwannomas, meningiomas and ependymomas. These tumours may occur spontaneously or as a part of the hereditary disease Neurofibromatosis type 2 (NF2). Current therapies, surgery and radiosurgery, are not fully effective and new drug treatments are urgently needed. Schwannoma is the most common Merlin-deficient tumour, a hallmark for NF2 and a model for all other Merlin-deficient tumours. Therefore, to study Merlin-deficient tumours and to test different drugs we have developed a schwannoma in vitro cell model. Using this model we have previously identified several targets and tested various drugs including Sorafenib, which we have in phase 0 clinical trials on NF2 patients. Our preliminary data suggest that a promising target for Merlin-deficient tumours is one group of endogenous retroviruses called HERVK (Human Endogenous Retrovirus type K). Endogenous retroviruses are viruses that have integrated themselves into germ-line chromosomes and thereby become part of human genome (8%). HERVK are overexpressed in several cancers and activate pathways known to be involved in schwannoma development such as NFkB, β-catenin, ERK and AKT. HERVK proteins are currently being investigated as potential immunotherapy targets for cancer and HIV. We find that HERVK envelope, capsid/gag, Rec and Np9 proteins are overexpressed in human primary schwannoma cells and tissues. Additionally, HERVK envelope and capsid proteins are released from schwannoma cells. HERVK envelope expression is Merlin dependent and both HERVK envelope and capcid/gag expression are transcriptionally and translationally regulated. Anti-HERVK antibodies reduced schwannoma proliferation, pERK/pAKT/ pFAK and cyclin D1 levels and increased expression of p53. Also, pre-incubation of schwannoma cells with anti-HERVK antibodies prior to treatment with Selumetinib potentiated drug’s efficiency. An HIV protease inhibitor with some potency for HERVK protease, Ritonavir, also decreased proliferation of schwannoma cells and increased the efficiency of Selumetinib, Sorafenib and BEZ235 when combined. We suggest that HERVK plays a relevant role in schwannoma and other Merlin-deficient tumours development.
Quantitative Assessment of PD-L1 Expression in Classical Hodgkin Lymphoma Suggests a Critical Role for Tumor Associated Macrophages in Suppressing Anti-Tumor Immunity
Authors: Christopher Daniel Carey, Courtney Connelly, Evisa Gjini, Margaretha GM Roemer, Edward Stack, Stephen Hodi, Margaret A. Shipp, Scott J. Rodig
Journal: Blood (2015)