tbuckley/cabot-search huggingface dataset:
Abstract 4411: DRAK1 overexpressed in head and neck cancer suppresses the TGF-β1 tumor suppressor activity in head and neck cancer cells
Authors: Kyung-Min Yang, WonJoo Kim, Jeong-Mi Lee, Seong-Jin Kim
Journal: Cancer Research (2014)

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and a highly malignant cancer associated with poor prognosis and low overall survival. Here, we describe a role of DRAK1 (DAP kinase-related apoptosis-inducing kinase 1) in head and neck cancer cells. DRAK1 is significantly overexpressed in primary head and neck tumors and cell lines. Overexpression of DRAK1 decreased the TGF-β1-induced transcriptional activity and expression of tumor suppressor target genes, including p15, p21, whereas DRAK1 silencing enhanced. Furthermore, endogenous depletion of DRAK1 enhanced the TGF-β1-induced cell growth inhibition and suppressed the tumorigenic ability of head and neck cancer cells in vivo. Interestingly, the gain- or loss-of-function of DRAK1 did not change the TGF-β1-induced phosphorylation of Smad2/3. DRAK1 specifically binds to Smad3 through its kinase domain, thereby blocking recruitment of Smad4 and translocation of Smad3 into nucleus. Thus, our findings suggest that aberrant expression of DRAK1 increases tumorigenic potential through the inhibition of TGF-β1 tumor suppressor activity in head and neck cancer cells. *This work was supported by a National Research Foundation grant of Korea (2009-0081756) funded by the Korea government. Citation Format: Kyung-Min Yang, WonJoo Kim, Jeong-Mi Lee, Seong-Jin Kim. DRAK1 overexpressed in head and neck cancer suppresses the TGF-β1 tumor suppressor activity in head and neck cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4411. doi:10.1158/1538-7445.AM2014-4411
Abstract 1722: Investigating resistance to AZD9291
Authors: Cath Eberlein, Laura Ratcliffe, Lucy O'Brien, Katie Al-Khadimi, Henry Brown, Paul Fisher, Daniel Stetson, Zhongwu Lai, Gayle Marshall, Claire Barnes, Kenneth Thress, Brian Dougherty, William Pao, Darren Cross
Journal: Cancer Research (2014)

Abstract First- and second-generation EGFR TKIs are established first line therapy for patients with NSCLC with activating mutations in EGFR. Unfortunately, patients ultimately develop disease progression with acquisition of a second-site EGFR T790M mutation in more than half of cases. This has led to the development of third generation EGFR TKIs which inhibit both the EGFRm+ and T790M mutations in preclinical models and are showing activity in TKI-resistant patients in Phase I studies. Despite the potential improvements brought by third generation EGFR-TKIs, advanced EGFRm+ tumor cells will still remain highly adaptable and the inevitability of further resistance will limit the effectiveness of these drugs. As such, the identification of resistance mechanisms to these agents is essential to guide future therapeutic strategies and identify novel:novel combinations. To interrogate resistance to AZD9291, we have generated panels of EGFRm+ cell lines resistant to gefitinib (first generation TKI) and EGFRm+ and EGFRm+/T790M cell lines resistant to afatinib and AZD9291 (second and third generation TKIs, respectively). Subsequently, we characterised the cell lines using a variety of molecular profiling techniques including Next Generation Sequencing (NGS), Affymetrix gene expression analysis, and phenotypic profiling following pharmacological modulation by small molecule inhibitors of canonical signaling pathways. The effects on cell survival across the range of resistant models by a panel of pathway inhibitors indicated that resistance to the EGFR inhibitors, in particular AZD9291, is frequently associated with increased sensitivity to selumetinib (AZD6244; ARRY-142886) (MEK1/2 inhibitor), suggesting that ERK signaling is commonly reactivated to circumvent inhibition of the EGFR pathway. Molecular characterisation of the panel of cell lines suggests a range of different resistance mechanisms may be responsible for reactivation of ERK signaling, including a decrease in negative regulators of ERK such as DUSP6 or an epithelial to mesenchymal transition consistent with previous observations. Collectively, these data suggest that combining an EGFR TKI with a MEK inhibitor could prevent or delay resistance and drive superior duration of benefit from these agents. Citation Format: Cath Eberlein, Laura Ratcliffe, Lucy O'Brien, Katie Al-Khadimi, Henry Brown, Paul Fisher, Daniel Stetson, Zhongwu Lai, Gayle Marshall, Claire Barnes, Kenneth Thress, Brian Dougherty, William Pao, Darren Cross. Investigating resistance to AZD9291. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1722. doi:10.1158/1538-7445.AM2014-1722
A temporal window of vulnerability for development of atrial fibrillation with advancing heart failure
Authors: Alexander Burashnikov, José M. Di Diego, Serge Sicouri, Michael Xavier Doss, Agapios Sachinidis, Hector Barajas‐Martínez, Dan Hu, Yoshino Minoura, N. Sydney Moise, Bruce G. Kornreich, Liguo Chi, Luiz Belardinelli, Charles Antzelevitch
Journal: European Journal of Heart Failure (2014)
Allogeneic stem cell transplantation as initial salvage for patients with acute myeloid leukemia refractory to high‐dose cytarabine‐based induction chemotherapy
Authors: Elias Jabbour, Naval Daver, Richard Champlin, Michael Mathisen, Betul Oran, Stefan Ciurea, Issa Khouri, A Megan Cornelison, Hady Ghanem, Marylou Cardenas‐ Turanzas, Uday Popat, Farhad Ravandi, Sergio Giralt, Guillermo Garcia‐Manero, Jorge Cortes, Hagop Kantarjian, Marcos de Lima
Journal: American Journal of Hematology (2013)

Outcomes of patients with acute myeloid leukemia (AML) who are refractory to high-dose Cytarabine (HiDAC)-based induction are dismal. Allogeneic hematopoietic stem cell transplantation (AHSCT) as initial salvage may be effective and potentially superior to conventional salvage chemotherapy. Eighteen percent (285 of 1597) of AML patients were primary refractory to HiDAC-based regimens at the MD Anderson Cancer Center between 1995 and 2009. AHSCT was the initial salvage in 28 cases. These patients were compared against 149 patients who received salvage chemotherapy, but never received AHSCT. Patients receiving salvage chemotherapy were older, had higher bone marrow blasts percentage, and higher incidence of unfavorable cytogenetics (P < 0.001). Median time from induction to AHSCT was 76 days. Objective response was achieved in 23 of 28 patients (82%) undergoing AHSCT. The incidence of grade III/IV acute and chronic graft versus-host-disease was 11% and 29%, respectively. Median follow up for living patients is 80 months. Median overall survival (OS) was 15.7 months and 2.9 months for AHSCT and chemotherapy, respectively (P < 0.001); the 3-year OS rates were 39% and 2%, respectively. ASHCT as initial salvage therapy was identified as an independent prognostic factor for survival in multivariate analysis (HR = 3.03; P < 0.001). Initial salvage therapy with AHSCT in patients with primary HiDAC refractory AML is feasible and may yield superior outcomes to salvage chemotherapy.
Increased activity of Lyn tyrosine kinase causes multiple chronic obstructive pulmonary disease-like changes in mouse
Authors: Wei Loon Lau, Erika Duan, Jonathan L. McQualter, Gary P. Anderson, Margaret L. Hibbs
Journal: European Respiratory Journal (2012)

Lyn is a member of the Src family of tyrosine kinases and was first discovered to be an key regulator of B cell activation. There are many studies now showing that Lyn also plays a role in the progression of myeloid leukemia and several types of epithelial cancer. The Lyn gain-of-function (Lyn up/up) mutant mouse was created to investigate putative proto-oncogenic roles of Lyn. Lyn up/up mice develop chronic lung inflammation and emphysema at young age. The extent of alveolar airspace enlargement in the Lynup/up mouse model is more severe than any other gene-targeted or smoke-induced mouse model of emphysema to date. Chronic lung inflammation, characterised by increase in macrophages, neutrophils and T cells and development of skeletal muscle wasting and osteoporosis in COPD patients were also observed in Lynup/up mice. Lung tumors have also been found is some aged mice although penetrance is low. Histological assessment of lungs in 4 week old Lyn up/up mice shows that alveolar epithelial cells are hyperplastic and there were a lack of blood vessels formation around the alveoli. There is also reduced numbers of apoptotic cells in the lung as detected by TUNEL assay. This suggests that alveolar airspace enlargement is not a result of emphysematous destruction caused by chronic inflammation but a possible attribute of perturbed signaling in endothelial and/or epithelial cells that needs further investigation. The complex process that leads to the occurrence of emphysema together with lung cancer is still not understood. The Lyn up/up mouse will be an excellent model to investigate the underlying co-determinant of the two seemingly opposite outcome of lung disease.
Abstract 18041: Dysregulated Fatty Acid Metabolism in Pulmonary Arterial Hypertension is Associated with Right Ventricular Steatosis and Lipotoxicity
Authors: Evan L Brittain, Megha Talati, He Zhu, James West, Joshua P Fessel, Niki Penner, Mitch Funke, Gregory D Lewis, Robert E Gerszten, Rizwan Hamid, Meredith E Pugh, Eric D Austin, John H Newman, Anna R Hemnes
Journal: Circulation (2014)

Introduction: The mechanisms of right ventricular (RV) failure in pulmonary arterial hypertension (PAH) are poorly understood. We have previously shown that heritable PAH is associated with RV lipotoxicity. Abnormalities in fatty acid metabolism have been described in experimental PAH, but systemic and myocardial fatty acid metabolism have not been well described in human PAH. We hypothesized that abnormal fatty acid metabolism in PAH is associated with altered peripheral lipid metabolism and lipotoxic cardiac steatosis. Methods and Results: We measured plasma free fatty acids (FFA) and acylcarnitine (fatty acid metabolites) profiles in PAH patients and age, gender, and body mass index-matched controls. In a transgenic murine model of PAH, we measured RV FAs and acylcarnitines. Using proton magnetic resonance spectroscopy we quantified in vivo myocardial triglyceride content in 6 PAH patients and 5 healthy controls. To test the functional consequences of lipid accumulation, we stained explanted human PAH ...
Childhood and adolescent cancer statistics, 2014
Authors: Elizabeth Ward, Carol DeSantis, Anthony Robbins, Betsy Kohler, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2014)

Abstract In this article, the American Cancer Society provides estimates of the number of new cancer cases and deaths for children and adolescents in the United States and summarizes the most recent and comprehensive data on cancer incidence, mortality, and survival from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries (which are reported in detail for the first time here and include high‐quality data from 45 states and the District of Columbia, covering 90% of the US population). In 2014, an estimated 15,780 new cases of cancer will be diagnosed and 1960 deaths from cancer will occur among children and adolescents aged birth to 19 years. The annual incidence rate of cancer in children and adolescents is 186.6 per 1 million children aged birth to 19 years. Approximately 1 in 285 children will be diagnosed with cancer before age 20 years, and approximately 1 in 530 young adults between the ages of 20 and 39 years is a childhood cancer survivor. It is therefore likely that most pediatric and primary care practices will be involved in the diagnosis, treatment, and follow‐up of young patients and survivors. In addition to cancer statistics, this article will provide an overview of risk factors, symptoms, treatment, and long‐term and late effects for common pediatric cancers. CA Cancer J Clin 2014;64:83–103. © 2014 American Cancer Society.
Genome-wide mapping with biallelic markers in Arabidopsis thaliana
Authors: Raymond J. Cho, Michael Mindrinos, Daniel R. Richards, Ronald J. Sapolsky, Mary Anderson, Eliana Drenkard, Julia Dewdney, T. Lynne Reuber, Melanie Stammers, Nancy Federspiel, Athanasios Theologis, Wei-Hsien Yang, Earl Hubbell, Melinda Au, Edward Y. Chung, Deval Lashkari, Bertrand Lemieux, Caroline Dean, Robert J. Lipshutz, Frederick M. Ausubel, Ronald W. Davis, Peter J. Oefner
Journal: Nature Genetics (1999)
<scp>WT</scp>1 vaccination in <scp>AML</scp> and <scp>MDS</scp>: A pilot trial with synthetic analog peptides
Authors: Jason Brayer, Jeffrey E. Lancet, John Powers, Alan List, Lodovico Balducci, Rami Komrokji, Javier Pinilla‐Ibarz
Journal: American Journal of Hematology (2015)

Peptide vaccines are capable of eliciting immune responses targeting tumor-associated antigens such as the Wilms' Tumor 1 (WT1) antigen, often overexpressed in myeloid malignancies. Here, we assessed the safety, tolerability, and immunogenicity of a polyvalent WT1 peptide vaccine. Individuals with WT1-positive acute myeloid leukemia (AML) in first (CR1) or second (CR2) remission or with higher-risk myelodysplastic syndrome (MDS) following at least 1 prior line of therapy were vaccinated with a mixture of peptides derived from the WT1 protein, with sargramostim injections before vaccination to amplify immunogenicity. Six vaccinations were delivered biweekly, continuing then monthly until patients received 12 vaccinations or showed disease relapse or progression. Therapeutic efficacy was evaluated by progression-free and overall survival. Immune responses were evaluated by delayed-type hypersensitivity testing and T-cell IFNγ ELISPOT at specified intervals. In 16 patients who received at least one vaccination, 10 completed the planned course of six vaccinations and six continued for up to six additional monthly vaccinations. Vaccinations were well tolerated, with no patients discontinuing due to toxicity. One of two patients with high-risk MDS experienced a prolonged decrease in transfusion dependence. Two of 14 AML patients demonstrated relapse-free survival >1 year. Both patients were in CR2 at time of vaccination, with duration of their remission exceeding duration of their first remission, suggesting a potential benefit. Our WT1 vaccine was well-tolerated. The clinical benefit that we observed in several patients suggests engagement of a protective immune response, indicating a need for further trials.
Abstract 17843: Visceral Adipose Tissue Secretion of Adiponectin Decreases with Increased Body Mass Index
Authors: Lenore R Rengel, Brittaney Obi, Jon Gould, Matthew Goldblatt, Andrew Kastenmeier, James Wallace, Matthew Frelich, Kay Nicholson, Daisy Sahoo, Srividya Kidambi
Journal: Circulation (2014)

Introduction: Peripheral adiposity is associated with better metabolic health and higher plasma adiponectin (ADPN) levels. Since ADPN is secreted mainly by adipose tissue (AT), it is intriguing that higher visceral adipose tissue (VAT) is associated with lower ADPN levels and poor metabolic health. Hypothesis: We hypothesized that various AT depots differ in their ability to secrete ADPN. Methods: Paired AT samples (VAT and subcutaneous adipose tissue (SAT)) were collected from 19 subjects (10 women, 15 obese) undergoing elective abdominal surgery. The samples were cultured and the supernatant was collected after 24 hours. ADPN levels released into the supernatant from VAT and SAT were measured using multiplex methods. Subjects were defined as obese or non-obese (NO) based on BMI &gt; or ≤ 30kg/m2 respectively. Obese subjects were further classified as metabolically unhealthy obese (MUO) or metabolically healthy obese (MHO) based on presence or absence of type 2 diabetes mellitus, hypertension, or cardiovascular disease at the time of surgery. Results: Mean ADPN secretion levels from SAT and VAT were similar in NO subjects (17.3 ± 3.4 vs. 9.8 ± 13.0 ng/mL/mg, p=0.5) whereas the mean ADPN secretion was lower from VAT among obese subjects (15.9 ± 0.8 vs. 4.5 ± 0.2 ng/mL/mg, p=0.0002). ADPN secretion decreased from VAT (r=-0.16) and increased from SAT (r=0.33) with increased BMI (Fig.1). When MHO and MUO were compared, ADPN secretion from VAT in MHO was reduced only slightly (16.1 ± 8.2 vs. 4.0 ± 2.0 ng/mL/mg, p=0.07) whereas ADPN secretion was significantly reduced in MUO (15.9 ± 5.3 vs. 4.7 ± 4.6 ng/mL/mg, p=0.003). Conclusions: Reduced ADPN secretion from VAT in subjects with increasing BMI may explain lower circulating ADPN levels in obese individuals. Higher ADPN production from SAT and the relatively preserved secretion of ADPN from VAT may explain metabolic health in some obese individuals. Futures studies will help identify factors that control ADPN secretion from AT.
Henry Taylor Howatt John Erskine Malcolm Ronald George Milne William Francis O'Dwyer Jeffrey Richard Scholey
Authors: R Holmes, A. Hardie, J. M. Imray, H E Counihan
Journal: BMJ (1999)

# Henry Taylor Howatt {#article-title-2}

Consultant physician Manchester Royal Infirmary, 1948-76, and professor of gastroenterology University of Manchester, 1972-76 ( b Pittenweem, Fife, 1911, to parents who were both head teachers; q St Andrews 1933; MD (with honours and gold medal, FRCP; CBE), d 29 October 1998. Virtually the whole of his life was spent at the royal infirmary, except for the second world war, when he was physician specialist with the army in the Middle East, France, and Germany, reaching the rank of honorary lieutenant colonel. After the war Harry and colleagues demonstrated the physiological actions of pancreozymin and secretin in humans, and in a series of papers described their use in tests of pancreatic and gall bladder function. This enabled him to differentiate acute and chronic relapsing forms of pancreatitis and to chart the course of these diseases. These early results led to the formulation of the Marseilles Classification of Pancreatitis, and Harry became the first president of the European Pancreatic Club. Harry realised that gastroenterology would evolve into …
Rapid diagnosis of coccidioidomycosis by nested PCR assay of sputum
Authors: R. de Aguiar Cordeiro, R.S. Nogueira Brilhante, M.F. Gadelha Rocha, F.E. Araújo Mourn, Z. Pires de Camargo, J.J. Costa Sidrim
Journal: Clinical Microbiology and Infection (2007)
Political Activity of US Physicians—Reply
Authors: Russell L. Gruen, Eric G. Campbell, David Blumenthal
Journal: JAMA (2007)

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Strama - a Swedish working model for containment of antibiotic resistance
Authors: S Mölstad, O Cars, J Struwe
Journal: Eurosurveillance (2008)

The overall aim of Strama (The Swedish Strategic Programme Against Antibiotic Resistance) is to preserve the effectiveness of antibiotics in humans and animals. Strama is organised at two levels: a network of independent local multidis ciplinary groups in each county that provide prescribers with feedback on antibiotic use and resistance and implement guidelines; and a national executive working group funded by the government. To gain an insight into antibiotic use, Strama has conducted several large diagnosis prescribing surveys in primary care, in the hospital settings and in nursing homes. National antibiotic susceptibility data for Sweden and mandatory notification show that in recent years the proportion of Streptococcus pneumoniae with decreased sensitivity to penicillin V has stabilised (around 6 %), but the number of notified cases of meticillin-resistant Staphylococcus aureus (MRSA)has increased and ESBL-producing Enterobacteraceae have turned into an endemic situation. Still, Sweden is among the countries with the lowest rates of MRSA (<1 %), S. pneumoniae can still be treated with penicillin V and the rate of Escherichia coli-producingESBLs is below 5 %. Strama's activities have contributed to a steady decrease in antibiotic use from the mid 1990s until 2004(when total use slowly started to increase again) without measurable negative consequences. Regular collaboration with national and regional news media has been one of the key strategies.
Abstract 13274: Frailty is an Independent Prognostic Factor when Added to Existing Acute Ischemic Stroke Mortality Models
Authors: Mathew J Reeves, Heidi Sucharew, Jane Khoury, Kathleen Alwell, Charles Moomaw, Brett Kissela, Daniel Woo, Matthew Flaherty, Opeolu Adeoye, Pooja Khatri, Simona Ferioli, Dawn Kleindorfer
Journal: Circulation (2014)

Introduction: Frailty is a state of decreased reserve and cumulative decline in multiple physiologic systems. Several frailty measures have been developed but have not been considered in existing stroke mortality prediction models. We sought to determine whether frailty is an independent predictor when added to existing stroke mortality models. Methods: Clinical data from incident ischemic stroke admissions in the Cincinnati/ Northern Kentucky Stroke Study during 2005 were abstracted by research nurses. Using established methods, we developed a frailty index using 35 age-related deficits that included pre-stroke function, comorbidities, symptoms, and clinical and lab values at admission. The index was specified as the total number of deficits or frailty score (range 0 to 35). Two established stroke mortality prediction models - one for in-hospital mortality and one for 1-year mortality, were identified and applied to the data. The independent contribution of the frailty score (expressed as a 1 deficit increase) to these existing models was determined from the logistic regression models. Results: A total of 2092 ischemic strokes were included. The median age was 72 years, 22% black, 56% female, median NIHSS 4 (IQR 2, 7). In-hospital and 1-year mortality were 8.8% and 26%, respectively. The median frailty score was 6 (IQR 4, 9). Both existing models fit the data well; the model c-statistics were both high (0.877 and 0.808, respectively) (Table). The frailty score was independently associated with higher mortality in both models; a 1 unit increase in age-related deficits was associated with a 20% and 17% increase in the adjusted odds ratio of in-hospital and 1-year mortality, respectively. Conclusions: When added to existing mortality prediction models, a frailty score showed strong independent associations with mortality. These data suggest that adding frailty to stroke mortality prediction models could improve their predictive accuracy and clinical utility.