tbuckley/cabot-search huggingface dataset:
Multiparametric MRI evaluation of tumor response in patients with hepatic malignancies treated with loco-regional therapy.
Authors: I. R. Kamel, S. Bonekamp, D. K. Reyes, D. Bonekamp, T. Wahlin, J. H. Geschwind
Journal: Journal of Clinical Oncology (2010)

e14595 Background: We evaluated proton spectroscopy (1H-MRS), contrast-enhanced and diffusion-weighted MRI changes in hepatic tumors treated with loco-regional therapy. Methods: 44 patients (29 men; mean age 58 years) with hepatic malignancies were treated locally. MRI exams obtained before and after loco-regional therapy were analyzed retrospectively. Imaging criteria included change in tumor size, percentage of enhancement in the arterial and portal venous phases, diffusion-weighted imaging apparent diffusion coefficients (ADC) and choline concentration (CHO) by quantitative 1H-MRS. Response to treatment was grouped according to Response Evaluation Criteria in Solid Tumors (RECIST) and European Association for the Study of the Liver criteria (EASL). Statistical analysis used paired t-test, Fisher's exact test, univariate and multivariante Cox's proportional hazards models. Results: Partial response, according to RECIST and EASL, was achieved in 66% of the patients, 31% had stable disease and 3% of the patients showed progressive disease. Before treatment, the mean tumor size was 48.3 cm2 and mean enhancement in the arterial and portal venous phases were 50% and 70% respectively. The mean enhancement decreased to 30% and 40% respectively (p < 0.00005) after treatment. The tumor ADC increased from 0.0015 mm2/s before treatment to 0.0016 mm2/s after treatment (p < 0.14).As expected, ADCs for the normal appearing liver and spleen remained unchanged. The mean CHO of the tumors decreased from 9.42 mmol/kg to 3.68 mmol/kg after treatment (p < 0.008). Univariate Cox's proportional hazards model suggested that response to treatment according to EASL was 4 times more likely in patients whose CHO decreased after treatment and 3.5 times more likely in patients whose ADC increased after treatment. Multivariate Cox's proportional hazards model showed that a decrease in CHO and an increase in ADC after treatment were independently associated with a shorter time to response to therapy. Conclusions: Contrast-enhanced and diffusion-weighted imaging as well as hepatic choline levels by 1H-MRS can predict response to loco-regional therapy. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biocompatibles International, Boston Scientific, Genentech Biocompatibles International, Boston Scientific
Relapse after radical surgery for non-small cell lung cancer 2005-2009 – A retrospective quality management analysis
Authors: Niels-Chr. G. Hansen, Anja Ør Knudsen
Journal: European Respiratory Journal (2011)

National guidelines for post-therapy lung cancer care are about to be introduced in Denmark. At our hospital, “usual care” after radical surgery for non-small cell lung cancer (NSCLC) has previously been to suggest the patient to have a chest x-ray once a year. To prepare improved post-therapy care we have made a retrospective analysis of the 986 consecutive patients from the primary uptake area reported by our diagnostic unit to the Danish Lung Cancer Registry in the 5-year period 2005–2009. Of the 792 patients with NSCLC 227 (28.7%) were treated with curative intent. Out of these 153 (19.2% of all with NSCLC) had intended radical resection of the primary tumor and if needed chemotherapy, radiotherapy, and/or resection of a single secondary tumor to assure a radical primary treatment. Median age for the 75 women and 78 men was 66 years (range 37 to 85 years). Clinical stages I, II, IIIa, and IIIB+IV were found in 122, 19, 5, and 7 patients. Two patients died at day 14 and day 31 after surgery. Among the 151 remaining patients, we have until February 22, 2011 recorded a relapse in 62 patients and a new lung cancer in three patients. In one patient, the cancer was found at post mortem examination, in 48 patients clinical symptoms lead to the diagnosis while a scheduled control by chest x-ray, CT, PET-CT, bronchoscopy, or blood tests lead to the diagnosis in 16 cases. Twenty-eight patients (18.5%) had a relapse within one year from surgery. Median time to relapse after a scheduled test was 288 days against 478 days in patients diagnosed after symptoms. Scheduled post-therapy control for all NSCLC patients may considerably shorten the time to detection of a relapse.
Telomere Length Predicts Anaemia in Patients With Chronic Heart Failure and is Inversely Associated With Haemoglobin Levels
Authors: Liza S. Wong, Jardi Huzen, Pim van der Harst, Rudolf A. de Boer, Germaine F. Benus, Adriaan A. Voors, Wiek H. van Gilst, Veryan Codd, Nilesh J. Samani, Tiny Jaarsma, Dirk J. van Veldhuisen
Journal: Circulation (2009)
The Current State of Critical Limb Ischemia
Authors: Alik Farber, Robert T. Eberhardt
Journal: JAMA Surgery (2016)

<h3>Importance</h3> Chronic critical limb ischemia, marked by intractable lower extremity ischemic rest pain and tissue loss, is a highly morbid condition that leads to the loss of ambulation and decreased quality of life. It is associated with a high risk of limb loss and mortality and presents a significant economic burden to society. <h3>Objective</h3> To review the current state of epidemiology, pathophysiology, diagnosis, and treatment of critical limb ischemia. <h3>Evidence Review</h3> An extensive literature search of the subject matter was conducted on material published in English between 1980 and 2016; both landmark and recently published articles were evaluated. Articles were reviewed if they included the terms<i>critical limb ischemia</i>,<i>ischemic rest pain</i>,<i>gangrene</i>, or<i>extremity ulcers</i>. <h3>Findings</h3> Critical limb ischemia represents the end stage of peripheral arterial disease. Because peripheral arterial disease is most commonly caused by atherosclerosis, critical limb ischemia is heavily associated with smoking and diabetes. Revascularization is the cornerstone of therapy to prevent limb amputation, and both open vascular surgery and endovascular therapy play a key role in the treatment of patients with critical limb ischemia. However, few scientific data are available to identify the optimal revascularization strategy, which has led to a significant amount of variability and equipoise in the treatment of this condition. Medical therapy plays a significant role in optimizing coexistent cardiovascular risk factors and a limited role in improving limb outcomes in nonrevascularizable disease. <h3>Conclusions and Relevance</h3> Understanding critical limb ischemia and its treatment strategies is important for providing the best care for affected patients. Currently, ongoing randomized clinical trials in North America and the United Kingdom aim to provide data to support the best management of these patients.
miR-146b antagomir–treated human Tregs acquire increased GVHD inhibitory potency
Authors: Yunjie Lu, Keli L. Hippen, Amanda L. Lemire, Jian Gu, Weizhi Wang, Xuhao Ni, Parvathi Ranganathan, Bruce L. Levine, James L. Riley, Carl H. June, Laurence A. Turka, David H. Munn, Ramiro Garzon, Ling Lu, Bruce R. Blazar
Journal: Blood (2016)
Targeting BCL-2 and ABL/LYN in Philadelphia chromosome–positive acute lymphoblastic leukemia
Authors: Jessica T. Leonard, Joelle S. J. Rowley, Christopher A. Eide, Elie Traer, Brandon Hayes-Lattin, Marc Loriaux, Stephen E. Spurgeon, Brian J. Druker, Jeffrey W. Tyner, Bill H. Chang
Journal: Science Translational Medicine (2016)

The combination of venetoclax and dasatinib is synergistically effective in treating Philadelphia chromosome–positive ALL.
RAGs and BUGS: An alliance for autoimmunity
Authors: Rosita Rigoni, Fabio Grassi, Anna Villa, Barbara Cassani
Journal: Gut Microbes (2016)

Hypomorphic Rag mutations in humans cause Omenn Syndrome (OS) a severe immunodeficiency associated with autoimmune-like manifestations mediated by oligoclonal activated T and B cells. The clinical and immunological spectrum of OS presentation is extremely broad. However, the role played by environmental triggers in the disease pathogenesis remains largely unknown. We have recently shown in a murine model that gut microbiota has a substantial role in determining the distinctive immune dysregulation of OS. Here, we describe how dysbiosis and loss of T cell tolerance to commensals influence the expression of autoimmunity at the barrier site and beyond, and the disease hallmark hyper-IgE. We discuss how commensal antigens and gut-derived pathogenic T cells could potentially modulate skin immunity to determine cutaneous degenerations in OS. These mechanisms may have broader implications for a deeper understanding of the role of gut microbes in influencing barriers integrity and host physiology.
The Cost-Effectiveness of Antibiotic Prophylaxis for Patients at Risk of Infective Endocarditis
Authors: Matthew Franklin, Allan Wailoo, Mark J. Dayer, Simon Jones, Bernard Prendergast, Larry M. Baddour, Peter B. Lockhart, Martin H. Thornhill
Journal: Circulation (2016)

In March 2008, the National Institute for Health and Care Excellence recommended stopping antibiotic prophylaxis (AP) for those at risk of infective endocarditis (IE) undergoing dental procedures in the United Kingdom, citing a lack of evidence of efficacy and cost-effectiveness. We have performed a new economic evaluation of AP on the basis of contemporary estimates of efficacy, adverse events, and resource implications.A decision analytic cost-effectiveness model was used. Health service costs and benefits (measured as quality-adjusted life-years) were estimated. Rates of IE before and after the National Institute for Health and Care Excellence guidance were available to estimate prophylactic efficacy. AP adverse event rates were derived from recent UK data, and resource implications were based on English Hospital Episode Statistics.AP was less costly and more effective than no AP for all patients at risk of IE. The results are sensitive to AP efficacy, but efficacy would have to be substantially lower for AP not to be cost-effective. AP was even more cost-effective in patients at high risk of IE. Only a marginal reduction in annual IE rates (1.44 cases in high-risk and 33 cases in all at-risk patients) would be required for AP to be considered cost-effective at £20 000 ($26 600) per quality-adjusted life-year. Annual cost savings of £5.5 to £8.2 million ($7.3-$10.9 million) and health gains >2600 quality-adjusted life-years could be achieved from reinstating AP in England.AP is cost-effective for preventing IE, particularly in those at high risk. These findings support the cost-effectiveness of guidelines recommending AP use in high-risk individuals.
Visceral motor neuron diversity delineates a cellular basis for nipple- and pilo-erection muscle control
Authors: Alessandro Furlan, Gioele La Manno, Moritz Lübke, Martin Häring, Hind Abdo, Hannah Hochgerner, Jussi Kupari, Dmitry Usoskin, Matti S Airaksinen, Guillermo Oliver, Sten Linnarsson, Patrik Ernfors
Journal: Nature Neuroscience (2016)
A phase II trial of combined treatment of endoscopic mucosal resection (EMR) and chemoradiotherapy (CRT) for clinical stage I esophageal squamous cell carcinoma (ESCC): Japan Clinical Oncology Group study JCOG0508.
Authors: T. Tsuchida, M. Muto, K. Minashi, H. Ono, Y. Morita, R. Ishihara, I. Toshiro, H. Kawai, N. Boku, H. Fukuda
Journal: Journal of Clinical Oncology (2010)

TPS204 Background: Although many primary tumors of T1 esophageal cancers can be removed by endoscopy, EMR is usually indicated for mucosal (T1a) tumors and surgical resection with lymph node dissection is the standard treatment for submucosal (T1b) tumors because of latent lymph node metastasis. However, surgery often deteriorates patient's general condition. On the other hand, not a few patients with T1 tumor developed local recurrence after CRT. The aim of this study is to evaluate the efficacy and the safety of combined treatment of EMR for primary tumors and CRT for lymph node metastasis against clinical stage I ESCC. Methods: The eligibility criteria are: (1) histologically proven SCC of the thoracic esophagus, (2) diagnosed as T1b by endoscopic ultrasound, (3) absence of lymph node and distant metastasis by CT, (4) size of primary tumor < 5 cm, and circularity of esophageal lumen < 3/4, (5) age 20 < and < 75 years old, and (6) written informed consent. EMR is performed within 30 days from the registration, and additional treatment strategy is decided by the histological findings of the resected specimen. In cases of pT1a with negative resection margin and no vascular invasion, no additional treatment is given (Group A). In other cases, CRT is started at 29 to 70 days after EMR. The chemotherapy consists of continuous 5-FU (700 mg/m2/day, days 1-4, 29-32), and CDDP (70 mg/m2/day, day 1 and 29). The dose of radiotherapy is 41.4 Gy/23 Fr/5 weeks for cases with negative resection margin (Group B) and 50.4 Gy/28 Fr/5 weeks with boost on the primary site for the case with positive resection margin (Group C). The primary endpoint is a 3-year overall survival (OS) of Group B. The secondary endpoints are 3-year OS and progression free survival of all eligible patients, adverse events observed from EMR to CRT. The sample size of 82 for primary analysis with one- sided alpha of 0.05, the power of 90% is required, based on the expected and threshold 3-year OS as 90% and 80%. The study started form Dec 2006, 24 institutions of the Gastrointestinal Oncology Study Group in JCOG participate in this trial, and 75 patients have been enrolled by Jan 2010. No significant financial relationships to disclose.
Bioinspired Hydrogels to Engineer Cancer Microenvironments
Authors: Kyung Min Park, Daniel Lewis, Sharon Gerecht
Journal: Annual Review of Biomedical Engineering (2017)

Recent research has demonstrated that tumor microenvironments play pivotal roles in tumor development and metastasis through various physical, chemical, and biological factors, including extracellular matrix (ECM) composition, matrix remodeling, oxygen tension, pH, cytokines, and matrix stiffness. An emerging trend in cancer research involves the creation of engineered three-dimensional tumor models using bioinspired hydrogels that accurately recapitulate the native tumor microenvironment. With recent advances in materials engineering, many researchers are developing engineered tumor models, which are promising platforms for the study of cancer biology and for screening of therapeutic agents for better clinical outcomes. In this review, we discuss the development and use of polymeric hydrogel materials to engineer native tumor ECMs for cancer research, focusing on emerging technologies in cancer engineering that aim to accelerate clinical outcomes.
A pilot trial of oral topotecan (TPT) in patients with refractory advanced solid neoplasms expressing HIF-1α.
Authors: A. G. Duffy, G. Melillo, B. Turkbey, D. Allen, P. L. Choyke, C. Chen, M. Raffeld, J. H. Doroshow, A. Murgo, S. Kummar
Journal: Journal of Clinical Oncology (2010)

e13518 Background: HIF-1α is a transcription factor that mediates tumor angiogenesis and survival. Previous studies have demonstrated that daily administration of topotecan (TPT) - a topoisomerase-1 inhibitor - inhibits HIF-1α expression, angiogenesis, and tumor growth in human xenograft models. The primary aim of this study is to investigate whether TPT inhibits HIF-1α expression in human cancers. Methods: TPT was administered orally at 1.6 mg/m2 daily × 5 for 2 weeks, of a 28-day cycle, to patients with advanced solid tumors expressing HIF-1α in at least 10% of tumor cells. Tumor biopsies were obtained before and after 2 cycles of TPT. The primary endpoint was modulation of HIF-1α expression by IHC. mRNA expression of HIF-1α target genes was assessed by real-time PCR. Radiologic correlative studies (comprising 18FDG-PET, to assess tumor metabolism, and DCE-MRI, to assess blood flow and permeability) were obtained at baseline, after 2 weeks of therapy and post cycle 2. The statistical significance of the difference in HIF-1α values was determined by a Wilcoxon signed rank test. Results: 15 patients, median age 54 (range 25-70), were treated, with n=7 undergoing paired tumor biopsies and being evaluable for the primary endpoint. Disease types: melanoma, colon (n=3), ovarian (n=2), sarcoma (n=2), lung, bladder, adrenocortical (n=2), anal, pancreatic, head and neck. Three patients received TPT 1.6 mg/m2before protocol amended to 1.2 mg/m2because of dose-limiting G3 neutropenia and G4 thrombocytopenia. The median number of cycles received was 2. Only 5 patients proceeded beyond 2 cycles (maximum 6). The median reduction in HIF-1α by IHC was -7.5% (range -50.0 to +5.0%; p=0.16). 6 of 7 patients exhibited declines in K trans on DCE-MRI (p=0.13) and 5 of 7 exhibited Kep changes (p=0.45). One patient obtained a PR and 2 patients had SD. Conclusions: This is the first study evaluating HIF-1α modulation in tumor tissue as a primary clinical trial endpoint in cancer patients. Whilst trends in both HIF-1α modulation and radiologic correlates (kTrans alteration on DC-MRI) were seen, these were not statistically significant due to low patient numbers. No significant financial relationships to disclose.
Association between atopic dermatitis and attention deficit hyperactivity disorder in U.S. children and adults
Authors: M.A. Strom, A.B. Fishbein, A.S. Paller, J.I. Silverberg
Journal: British Journal of Dermatology (2016)

Atopic dermatitis (AD) is associated with chronic itch, allergic disease and sleep disturbance, all of which might increase the risk of attention deficit (hyperactivity) disorder (ADD/ADHD). Previous analyses have found a consistent association between AD and ADD/ADHD, although the underlying factors contributing to such an association remain underexplored. Additionally, the relationship has been underexplored in adults. To determine if childhood and adult AD and AD severity are associated with ADD/ADHD and to delineate the factors contributing to such an association. We analysed data on 354 416 children aged 2–17 years and 34 613 adults age 18+ years from 19 U.S. population‐based surveys, including the National Health Interview Survey 1997–2013 and the National Survey of Children's Health 2003/4 and 2007/8. In multivariate models adjusting for age, sex, sociodemographics, allergic disease and healthcare utilization, AD was associated with ADD/ADHD in both children [adjusted odds ratio (95% confidence interval), 1·14 (1·03–1·26)] and adults [1·61 (1·25–2·06)]. Children with both severe AD and only 0–3 nights of adequate sleep per week had much higher odds of ADD/ADHD [16·83 (7·02–40·33)] than those with 0–3 nights of adequate sleep per week [1·83 (1·47–2·26)] or mild–moderate AD alone [1·56 (1·22–1·99)]. AD was most strongly associated with severe ADHD. AD unaccompanied by other allergic disease was also associated with increased risk of ADD/ADHD in children. Among children with AD, history of anaemia, headaches and obesity were associated with even higher odds of ADD/ADHD. Asthma, insomnia and headaches increased the odds of ADHD in adults with AD, although underweight body mass index was protective. Atopic dermatitis is associated with increased odds of ADD/ADHD in adults and children. Several factors increase the risk of ADHD in adults and children with AD.
Changes in Gene Expression Profiles during Treatment with Erythropoetic Growth Factors in Myelodysplastic Syndromes.
Authors: Esther N. Oliva, Margherita Comis, Pasquale Iacopino, Mariella Cuzzola, Roberto Latagliata, Marco Danova, Bianca Rovati, Giovanni Spampinato, Giuliana Alimena, Ida Carmosino, Massimo Breccia, Francesco Nobile
Journal: Blood (2007)
The cohesin subunit Rad21 is a negative regulator of hematopoietic self-renewal through epigenetic repression of Hoxa7 and Hoxa9
Authors: J B Fisher, J Peterson, M Reimer, C Stelloh, K Pulakanti, Z J Gerbec, A M Abel, J M Strouse, C Strouse, M McNulty, S Malarkannan, J D Crispino, S Milanovich, S Rao
Journal: Leukemia (2016)
Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses
Authors: Nikhil K. Khankari, Xiao-Ou Shu, Wanqing Wen, Peter Kraft, Sara Lindström, Ulrike Peters, Joellen Schildkraut, Fredrick Schumacher, Paolo Bofetta, Angela Risch, Heike Bickeböller, Christopher I. Amos, Douglas Easton, Rosalind A. Eeles, Stephen B. Gruber, Christopher A. Haiman, David J. Hunter, Stephen J. Chanock, Brandon L. Pierce, Wei Zheng
Journal: PLoS Medicine (2016)

Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.