tbuckley/cabot-search huggingface dataset:
PTH-082 Dysregulated polyamines in the inflammatory bowel disease gut – a novel therapeutic target
Authors: J Bailey
Journal: Gut (2017)

IntroductionPolyamines (spermidine and spermine) are amino acid derivatives, critical for the maintenance of intestinal mucosal integrity, regulating inflammation and promoting mucosal healing. Levels of polyamines have been shown to be dysregulated in inflammatory bowel disease (IBD) patients; in c
Abstract #2507: Upregulated nicotinic receptors are associated with systemic increase in stress neurotransmitters and cAMP, induction of p-CREB and p-ERK and suppression of GABA in NNK-induced adenocarcinoma of the lung and pancreas.
Authors: Hussein Al-Wadei, Hildegard Schüller
Journal: Cancer Research (2009)

Small airway-derived pulmonary adenocarcinoma (PAC) and pancreatic ductal adenocarcinoma (PDAC) are common human cancers and smoking is a risk factor for both. Emerging research has identified cAMP signaling stimulated by the stress neurotransmitters adrenaline and noradrenaline as stimulators of PAC and PDAC. We have shown that the inhibitory neurotransmitter \#947;-aminobutyric acid (GABA) blocks the cAMP-dependent proliferation and migration of PAC and PDAC cells in vitro. The nicotine-derived nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent mutagen and carcinogen. NNK is also an agonist for nicotinic acetylcholine receptors (nAChRs). These receptors are central regulators that control the synthesis and release of neurotransmitters, growth factors, angiogenic factors and inflammatory mediators. The alpha7-nAChR stimulates the synthesis and release of adrenaline and noradrenaline in the brain and from nerve endings in all organs and tissues. The alpha4beta2-nAChR stimulates the synthesis and release of GABA that is expressed in most mammalian cells. While signal transduction events downstream of nAChRs expressed in cancer cells have been extensively studied, the systemic effects of these receptors on cancer have been largely ignored. Using hamster models of NNK-induced PAC and PDAC, we have tested the hypothesis that in analogy to chronic effects of nicotine in the brain, NNK may modulate the alpha7 and alpha4beta2-nAChR, causing a systemic increase in stress neurotransmitters and decrease in GABA. In support of our hypothesis, we found significant increase in serum adrenaline/noradrenaline and increased cAMP in the cellular fraction of blood from NNK treated hamsters. The GABA synthesizing enzyme glutamate decaboxylase 65 (GAD65) and GABA were suppressed in NNK-induced PACs and PDACs, whereas protein expression of the alpha7nAChR, alpha4-nAChR as well as p-CREB and p-ERK1/2 were upregulated. In analogy to the chronic effects of nicotine on brain cells, these data suggest that chronic exposure to NNK upregulates both investigated nAChRs while additionally desensitizing the alpha4beta2-nAChR, resulting in increased levels of cancer stimulating stress neurotransmitters and suppressed inhibitory GABA. Collectively, these findings suggest, for the first time, that NNK-induced alterations in regulatory nAChRs may contribute to the development of smoking-associated PAC and PDAC by disturbing the systemic balance between cancer stimulating and inhibiting neurotransmitters.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2507.
Gorham-Stout Disease Affecting the Mandible
Authors: Soo Bin Park, Joon Young Choi, Soo Jeong Kim
Journal: Clinical Nuclear Medicine (2017)

We present images of a 13-year-old boy with Gorham-Stout disease affecting the mandible. Initial bone scintigraphy showed poor visualization of 99mTc-methylene diphosphonate (99mTc-MDP) uptake in the mandible body. However, abnormally increased 99mTc-MDP uptake was noted in the bilateral mandibular rami. In the follow-up examination a year later, bone scintigraphy indicated that the disease had progressed to the bilateral mandibular rami with no uptake. In addition, massive osteolysis of the mandible was noted that had progressed since the initial computed tomography. This report suggests that bone scintigraphy could be a useful imaging tool to evaluate disease activity and determine treatment response.
BRAF, KIT, and NRAS testing patterns and results in metastatic melanoma.
Authors: Amy P Abernethy, Chi Fung, Paul Richardson, Daniel S Eisenberg, Dominique Connolly, May Terry, Ross N Feinstein, Melisa Tucker, Catherine Miller, Leonardo Viana Nicacio
Journal: Journal of Clinical Oncology (2015)

e20089 Background: BRAF and other potentially-targetable mutations in metastatic melanoma (mM) inform choice of systemic therapy. Real-world patterns of testing and mutation rates in the United States (US) are poorly described. We studied BRAF, KIT and NRAS testing patterns in a large, longitudinal, real-world database. Methods: This was a retrospective, observational study from 118 community oncology clinics. Data were derived from structured (e.g., demographics) and unstructured (e.g., biomarkers) EMR sources; chart abstraction of unstructured sources was conducted as needed. Patients (pts) were eligible to be included for analysis if diagnosed with mM on or after 1/1/11, with at least two visits between 1/1/13 and 12/31/14. mM diagnoses were confirmed by review of physician notes and pathology/radiology reports; pts with non-skin melanoma or those with no evidence of metastatic disease were excluded. Results: The cohort comprises 760 mM pts. Information about initial diagnosis, date of metastatic diagnosis, and BRAF testing was complete in 100%, 99% and 100% of the pts, respectively. Median age was 67; 64% were male. Overall, 86% of pts were tested for BRAF, 14% for KIT and 7% for NRAS. The testing rate for BRAF mutations was relatively stable between 2012-14 (85-88%). Among tested pts, BRAF was mutated in 43%; results were inconclusive in 3%. BRAF mutation rates were higher with younger age: < 40y 69%; 41-50y 63%; 51-60y 50%; 61-70y 42%; > 70y 30%. Among BRAF-tested pts 65% pts were male; among untested, 58% were male. BRAF testing rates by region were similar: West 89%, Northeast 86%, Southeast and Midwest 85%. Among tested pts, 11% had KIT mutations and 16% had NRAS mutations. Conclusions: US testing patterns demonstrate fast and stable adoption of BRAF testing in mM. BRAF mutation rates are consistent with the published literature, including the observation of higher mutation rates among younger patients. Currently, KIT and NRAS testing is sparsely performed, with few mutations observed.
Distribution and determinants of patient satisfaction in oncology with a focus on health-related quality of life
Authors: C. G. Lis, M. Rodeghier, D. Gupta
Journal: Journal of Clinical Oncology (2009)

e17578 Background: Cancer patients usually undergo extensive and debilitating treatments, which makes patient satisfaction with care in oncology an important health care assessment measure. We conducted a study to examine patients’ experiences with the care they receive and to investigate the clinical, demographic and quality of life (QoL) factors that can predict satisfaction in a large heterogeneous sample of cancer patients. Methods: A case series of 538 cancer patients treated at Cancer Treatment Centers of America (CTCA) at Midwestern and Southwestern Regional Medical Centers between August 2006-December 2007. A patient satisfaction questionnaire developed in-house by CTCA was used. The questionnaire covered the following dimensions of patient satisfaction: hospital operations and services, physicians and staff, and patient endorsements for themselves and others. QoL was assessed using EORTC QLQ-C30. The available clinical, demographic and QoL factors were evaluated for predictive significance using univariate (t-test or chi-square test) and multivariate logistic regression. Results: The response rate for this study was 24.4%. The mean age of our patient population was 54.1 years (SD = 10.5, range 17–86), with a slight preponderance of females (57.2 %). Breast cancer (n = 124, 23.0 %) and lung cancer (n = 101, 18.8%) were the most frequent cancer types. 481 (89.4%) patients were “very satisfied” with their overall experience with CTCA. Age and several QoL function and symptom scales were predictive of satisfaction upon univariate analysis. However, in the multivariate modeling, only those with a score above the median on the fatigue measure (i.e., worse fatigue) had reduced odds of 0.28 of being “very satisfied” with CTCA (p = 0.03). Conclusions: We found that fatigue was an independent significant predictor of patient satisfaction. This finding argues for special attention and programs for cancer patients who report higher levels of fatigue. Such efforts will help lessen the effect of fatigue on their daily functioning, and may increase their satisfaction with treatment. No significant financial relationships to disclose.
DECREASED AVERAGE POWER OF THE HIP EXTERNAL MUSCLES AS A RISK FACTOR FOR THE DEVELOPMENT OF LOWER EXTREMITY INJURY IN WOMEN: A PROSPECTIVE STUDY
Authors: Ruth Verrelst, Damien Van Tiggelen, Roel De Ridder, Erik Witvrouw
Journal: British Journal of Sports Medicine (2017)

Background Attention has turned into the role of proximal risk factors in the development of lower extremity (LE) injury. Objective To prospectively identify hip strength associated risk factors contributing to the development of LE injury. Design Prospective cohort design. Setting Department of Physical Education at the University of Ghent, Belgium. Participants Ninety-four healthy, female physical education students aged 19.53±1.07 years were tested. Assessment of Risk Factors Testing included isokinetic hip strength measurements of abductors, adductors, internal rotators and external rotators. Main Outcome Measurements The LE injury follow-up of the subjects was assessed using a weekly online questionnaire and a three-monthly retrospective control questionnaire. Lower extremity injury was diagnosed by an experienced M.D. (Doctor of Medicine). Cox regression analysis was used to identify the potential risk factors for the development of LE injury. Results Thirty-four subjects were diagnosed with LE injury during follow-up. The results of this study identified that decreased average power (AVP) ( P =0.031) for concentric external rotation strength was found to be a significant risk factor for LE injury. No other hip strength parameters were found to be significant contributors to the development of LE injury. Conclusions Decreased AVP of the hip external muscles was identified as a significant predictor for LE injury in females, whereas no peak torque parameters were found to be of predictive value. A stabilizing muscle group such as the gluteal muscle group might be more challenged in a functional outcome measure then in a peak outcome measure. AVP might be therefore be considered as a more accurate parameter to evaluate strength of stabilizing muscles.
The effect of the CXCR7 inhibitor CCX662 on survival in the ENU rat model of glioblastoma.
Authors: Karen Ebsworth, Matthew J. Walters, Linda S Ertl, Yu Wang, Penglie Zhang, Jay P Powers, Timothy J. Sullivan, Juan C. Jaen, Martin Brown, Thomas J. Schall
Journal: Journal of Clinical Oncology (2012)

e13580 Background: Glioblastoma (GBM) is the most common form of malignant brain cancer. Despite aggressive therapy, consisting of radiotherapy, surgical resection, and chemotherapeutic treatment, mean survival from time of diagnosis remains little more than one year. The chemokine receptor CXCR7 is highly expressed on both human glioma cells and tumor-associated vasculature, and may play a key role in tumor growth and survival. Methods: The in vitro activity of the CXCR7 antagonist CCX662 was determined using radioligand binding assays and trans-endothelial migration assays. The therapeutic effects of CCX662 were investigated in the ENU-induced rat model of GBM in combination with radiotherapy. Results: CCX662 is a highly potent and selective small molecule inhibitor of CXCR7. CCX662 inhibits the binding of 125 I-CXCL12 to CXCR7 with an IC 50 of 9 nM in buffer, and displays minimal serum shift with an IC 50 of 18 nM in 100% human serum. CCX662 inhibits the CXCR4-directed trans-endothelial migration of CXCR4+/CXCR7+ NC37 cells towards CXCL12 (SDF1) with an IC 50 of 106 nM. CCX662 also potently inhibits binding of 125 I-CXCL12 to rat CXCR7 in the presence of 100% rat serum with an IC 50 of 14 nM. In vivo inhibition of CXCR7 with CCX662, in concert with radiotherapy, results in a significant extension of survival time in the ENU-induced rat model of GBM. The median survival time for rats (reflective of GBM tumor progression) treated with the combination of irradiation and CCX662 was 234 days compared with 160 days for untreated rats (p&lt;0.01) or compared with 174 days for rats given irradiation plus vehicle (p&lt;0.01). As expected for a non-cytotoxic drug, dose-range finding 14-day toxicology studies in rats and dogs have demonstrated large (&gt; 10 and 25-fold, respectively) safety margin relative to highly effective levels of the drug. Conclusions: CCX662 is a highly selective and potent small molecule inhibitor of CXCR7 with profound, therapeutic benefit in an aggressive rodent model of GBM. These data indicate that inhibition of CXCR7, using CCX662, may be a promising strategy for the treatment of glioblastoma.
02.10 X-linked mirnas associated with gender differences in rheumatoid arthritis
Authors: Olfa Khalifa, Yves-Marie Pers, Rosana Ferreira, Audrey Sénéchal, Christian Jorgensen, Florence Apparailly, Isabelle Duroux-Richard
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Aim</h3> The majority of auto-immune diseases predominate in females. Rheumatoid arthritis (RA) is one of these diseases for which female are three times more affected than men. MicroRNAs have emerged as crucial regulators of the immune system, and have been reported abnormally expressed in RA. As protein-encoding genes, miRNA-encoding genes can be affected by nucleotide single polymorphisms (SNPs) that could affect their expression levels in disease. We aimed at quantifying the expression level of miRNAs located on the X chromosome and at identifying whether differences are associated with disease and/or sex. <h3>Materials and methods</h3> A case–control study of 21 RA patients and 22 age- and sex-matched healthy controls was performed on peripheral blood mononuclear cells. Extraction of total RNA and DNA was performed and the expression level of 14 X-linked miRNAs quantified using real time quantitative polymerase chain reaction. Two FoxP3 polymorphisms were genotyped using the Sanger sequencing method. An analysis of expression quantitative trait loci (eQTL) was performed to detect transcriptional regulatory relationships between X-located miRNA expression levels and 2 single nucleotide polymorphisms in FOXP3 gene associated with RA susceptibility. <h3>Results</h3> We showed that miR-221, miR-222, miR-532, miR-106a and miR-98 expression levels were significantly different between RA and controls only when stratifying according to the sex. Furthermore, the expression level of 4 miRNAs (miR-222, miR-532, miR-98, miR-92a) was significantly different between RA female and male. We performed an eQTL analysis and showed a significant gender effect of the FoxP3 promoter polymorphism rs3761548A/C on miR-221, miR-222 and miR-532 expression levels, and of the FoxP3 polymorphism rs2232365A/G on miR-221 expression level in PBMC of RA patients. <h3>Conclusion</h3> These data further support the involvement of the X chromosome in RA susceptibility. X-linked miRNAs, in the context of sex differences, might provide novel insight into new molecular mechanisms and potential therapeutic targets in RA for disease treatment and prevention.
Abstract 18367: Echocardiographic Assessment of Myocardial Wall Stress to Risk Stratify Patients With Heart Failure
Authors: Natdanai Punnanithinont, Zaid Said, Pratik Patel, Alonzo Diaz, Umesh Sharma
Journal: Circulation (2016)

Introduction:  Heart failure (HF) is the most common cause of rehospitalization in the US and is associated with high morbidity and mortality. These high rates were partly due to the lack of reliable predictors.   Hypothesis:  Left ventricular (LV) wall stress is one of the major factors that determine myocardial oxygen consumption and contribute to ventricular remodeling. It is directly proportional to LV wall tension and inversely proportion to LV wall thickness. The role of LV wall stress from echocardiogram and HF readmission has never been studied.   Methods:  We prospectively enrolled the study participants of age 18 or older who were admitted to Buffalo General Medical Center and whom echocardiography were ordered. Exclusion criteria were patients with severe valvular diseases and poor quality study. LV wall stress measurement was calculated according to Laplace’s equation from mid-cavity parasternal short axis view of transthoracic echocardiogram. The primary endpoints include 30 day readmission, 30 day and 1 year mortality which were abstracted from the electronic medical record and confirmed with follow up calls. Since there have been no established cut-points for LV wall stress, it was categorized to be high or low comparing to the mean from study participants.   Results:  The median of LV systolic and diastolic wall stress were 62.84 and 10.10 mmHg. There were 109 study participants enrolled in the study and currently 19 patients completed 1 year follow up. Between high and low systolic LV wall stress, there were no significant differences in 30 day readmission (20.41% vs 27.77% p-value 0.44) , 30 day mortality (2.00% vs 4.35% p-value 0.51) and 1 year mortality (30.00% vs 44.44% p-value 0.51). Between high and low diastolic LV wall stress, there were no significant differences in 30 day readmission (28.26% vs 16.67% p-value 0.19), 30 day mortality (4.17 % vs 2.33% p-value 0.62) and 1 year mortality (28.57% vs 33.33% p-value 0.85).   Conclusions:  High LV systolic and diastolic wall stress were not associated with 30 day readmission, 30 day and 1 year mortality; however higher 30 day readmission and mortality were observed in patients with high diastolic LV wall stress. Further study is needed to further advance our understanding of LV wall stress and readmission risk.
radiooncologyのためのナノ粒子:ミッション,ビジョン,挑戦【Powered by NICT】
Authors: A Kunz-Schughart Leoni, Dubrovska Anna, Peitzsch Claudia, Ewe Alexander, Aigner Achim, Schellenburg Samuel, H Muders Michael, Hampel Silke, Cirillo Giuseppe, Iemma Francesca, Tietze Rainer, Alexiou Christoph, Stephan Holger, Zarschler Kristof, Vittorio Orazio, Kavallaris Maria, J Parak Wolfgang, Maedler Lutz, Pokhrel Suman
Journal: Biomaterials (2017)
Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study
Authors: Michael Crump, Sattva S. Neelapu, Umar Farooq, Eric Van Den Neste, John Kuruvilla, Jason Westin, Brian K. Link, Annette Hay, James R. Cerhan, Liting Zhu, Sami Boussetta, Lei Feng, Matthew J. Maurer, Lynn Navale, Jeff Wiezorek, William Y. Go, Christian Gisselbrecht
Journal: Blood (2017)
08.30 Histological features of synovial membrane of overweight/obese naive rheumatoid arthritispatients: correlations between inflammatory resident cells, bmi and response to therapy
Authors: Stefano Alivernini, Barbara Tolusso, Luca Petricca, Clara Di Mario, Maria Rita Gigante, Laura Bui, Gabriele Di Sante, Roberta Benvenuto, Anna Laura Fedele, Gianfranco Ferraccioli, Elisa Gremese
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Obesity is an independent risk factor for Rheumatoid Arthritis (RA) influencing disease course and treatment response. Despite animal models, little is known about synovial tissue composition of overweight/obese RA patients at disease onset. The aim of the study was to investigate the histological features of naive RA patients based on Body Mass Index (BMI) category and its association with treatment response. <h3>Materials and methods</h3> One-hundred RA patients [(57 DMARDs naive and 43 Methotrexate (MTX) no responder] were enrolled and underwent synovial tissue biopsy. At study entry RA patients were divided based on BMI value (BMI &lt;25kg/m<sup>2</sup>=normal weight, BMI &gt;25kg/m<sup>2</sup>=overweight and BMI &gt;30 kg/m<sup>2</sup>=obesity). Immunohistochemistry for CD68<sup>+</sup>, CD21<sup>+</sup>, CD20<sup>+</sup> and CD3<sup>+</sup> cells was performed. Each naive RA patient was treated according to the treat to target (T2T) strategy and followed for 12 months. <h3>Results</h3> Among the whole RA cohort, there were no significant differences in terms of demographic, immunological and clinical characteristics comparing naive to treatment and MTX no responder RA patients. However, considering naive to treatment RA, patients with BMI &gt;30 kg/m<sup>2</sup> showed more likely follicular synovitis (78.6%) than normal weight RA (39.1%; p=0.02). Moreover, BMI value directly correlated with synovial aggregate grade (R=0.311; p=0.02) and histological scores of CD21<sup>+</sup> (R=0.344; p=0.01), CD20<sup>+</sup> (R=0.295; p=0.03) and CD3<sup>+</sup> cells (R=0.256; p=0.05) in naive RA. In particular, ACPA<sup>-</sup> overweight/obese naïve RA patents showed higher frequency of follicular synovitis compared to ACPA<sup>-</sup> normal weight naïve RA patients (p&lt;0.05). Conversely, considering MTX no responder RA patients, there was no significant difference in terms of synovial inflammation based on different BMI categories. However, overweight/obese MTX no responder RA showed lower frequency of follicular synovitis (48.8%) compared to overweight/obese naive RA (70.6%; p&lt;0.05). Finally, regardless to the synovial inflammatory pattern (follicular vs diffuse), naive overweight/obese RA patients showed a worse clinical response to T2T strategy compared to normal weight naive RA at 6 and 12 months follow-up respectively (p&lt;0.05 for both). <h3>Conclusions</h3> Overweight and obesity are risk factors associated with higher degree of histologically proven synovitis and BMI status influences response rate to T2T regimen regardless to the synovial pattern in naive RA patients.
Fatal illnesses associated with a new world arenavirus - California, 1999-2000
Authors: R. G. Byrd, L. A. Cone, B. C. Commess, D. Williams-Herman, J. M. Rowland, B. Lee, M. W. Fitzgibbons, C. A. Glaser, Michele T Jay-Russell, Cl Fritz, M. S. Ascher, M. Cheung, V. L. Kramer, K. Reilly, D. J. Vugia, C. F. Fulhorst, M. L. Milazzo, R. N. Charrel
Journal: JAMA (2000)