tbuckley/cabot-search huggingface dataset:
Abstract 2244: The M-SKIP Project: an international pooled-analysis on melanocortin-1 receptor (MC1 R) variants and skin carcinogenesis
Authors: Sara Gandini, Alessandra di Pietro, Patrick Maisonneuve, Philippe Autier, Maria Concetta Fargnoli, José C. García-Borrón, Jiali Han, Peter A. Kanetsky, Maria Teresa Landi, Julian Little, Julia Newton-Bishop, Francesco Sera, Sara Raimondi
Journal: Cancer Research (2011)

Abstract Background: MC1R is one of the major genes involved in the determinism of skin pigmentation. The role of MC1R variants in skin carcinogenesis was previously investigated by a meta-analysis of 18 published studies. Although the results were informative, published data were not enough to deeply investigate the specific contribution of each MC1R variant on skin cancer development. Aim: The M-SKIP Project aims to perform an international collaborative pooled-analysis on the role of MC1R variants in skin carcinogenesis, using individual patient data. The main endpoint is skin cancer. Secondary endpoints are phenotypic characteristics involved in skin carcinogenesis, e.g. freckling. Methods and Patients: An Advisory Committee of investigators with great expertise in melanoma and genetic research was established. The authors of appropriate papers were invited to provide their original published and unpublished data. Preliminary results: Up to February 2010, 27 out of 35 contacted investigators (77%) agreed to join the M-SKIP Project. Thanks to the positive response obtained up to now, we estimate to receive data on around 6,500 melanoma cases, 1,500 non-melanoma skin cancer cases and 13,000 controls. So far, we have already received data on 2,683 melanoma cases, 1,364 non-melanoma skin cancer cases and 4,340 controls from 15 investigators internationally. After quality controls, data are inserted in a central database, and pooled-analysis will be performed in order to evaluate: (1) the association between MC1R variants and skin cancer overall, and by skin cancer type; (2) the association between MC1R variants and phenotypic characteristics under study; (3) MC1R-phenotype interaction in skin cancer risk. In addition, stratified analysis will be performed to understand the independent and dependent role of MC1R variants in skin cancer development by phenotypic characteristics. Conclusion: The pooled analysis approach applied in such a setting is particularly useful because it will help reaching firm conclusions even in sub-group and interaction analyses, controlling for important confounders. This data-bank will represent a reference and guide for all investigators working in this research field. Collaboration within investigators would significantly improve the knowledge and accelerate our understanding of the role of MC1R variants in skin carcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2244. doi:10.1158/1538-7445.AM2011-2244
P5-13-10: Discordance of Estrogen Receptor and HER-2/neu Status Can Be Seen between First and Subsequently Biopsied Metastatic Lesions in Breast Cancer.
Authors: EE Lower, D Kennedy
Journal: Cancer Research (2011)

Abstract Background We have previously reported discordance between primary and first metastasis for both estrogen receptor (ER) and HER-2/neu (HER 2) status (Breast Cancer Res Treat 2005;90:65–70 and Breast Cancer Res Treat 2009;113:301–6). Because biomarker status is the primary determinant for targeted therapy, changes in biomarkers can impact recommendations for systemic treatment. Materials and Methods: In order to evaluate the possibility of further discordance with the development of additional metastatic sites, we examined the ER and HER 2 status of primary and first and subsequently biopsied breast cancer metastasis. In most cases, the subsequent site of metastasis was the second detected metastasis. Pathology reports were reviewed from 65 patients with biopsy proven first and additional metastasis; however, immunostain results were not available for all three timepoints for all patients. Sites of biopsied metastasis included lung, liver, bone, chest wall, and central nervous system. Results: The time between the initial diagnosis and first metastasis was 102 (3-676) months [Median (Range)], and the time between the first and subsequent metastasis was 60 (6-273) months. For ER, there was discordance between the primary lesion and either the first or subsequent metastasis in 18 of 65 cases (27.7%). Discordance of the ER occurred between the first and subsequent metastasis in 12 (18%) of cases. Three patterns of ER discordance occurred in these 12 cases: 4 cases of both primary and first metastasis negative with subsequent metastasis positive; 3 cases of primary positive, first metastasis negative, and subsequent metastasis positive, and 5 cases of primary and first metastasis positive and subsequent metastasis negative. For HER 2, discordance was detected between the primary and either first or subsequent metastasis in 11 of 36 cases (30.6%). Further discordance between the first and subsequent metastatic lesions occurred in 8 of 51 (16%) of cases. Conclusions: A significant level of discordance for either ER or HER 2 was detected between first and subsequent metastatic breast cancer lesions. For breast cancer patients with new metastasis, consideration of reevaluating ER and HER-2/neu status may be worthwhile. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-10.
SAT0180 Subclinical Inflammation in Rheumatoid Arthritis (RA) in Clinical Remission, Lack of Association between Cytokines Level and Ultrasound-Defined Synovitis:
Authors: C. Hernández Díaz, M. Robles-San Roman, A. Vargas, A. Lopez-Macay, M.G. Santamaria Olmedo, A.G. Lopez Reyes, C. Pineda, L. Ventura Rios
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The presence of subclinical inflammation promotes the progression of morphostructural joint damage in RA patients. Currently, clinical remission is based on the count of swollen and painful joints associated with acute phase reactants. Adding an image technique like grey scale (GS) US and power Doppler (PD) increases the capability to detect active synovitis. There are no studies on the association between active synovitis as defined by PD and more specific markers of inflammation like cytokines in patients with RA in clinical remission <h3>Objectives</h3> To identify subclinical synovitis in patients with RA in clinical remission using US and to characterize the biological profile of this group of patients by determining inflammatory cytokines <h3>Methods</h3> RA patients in clinical remission according to ACR/EULAR criteria were enrolled. Clinical evaluation was performed and DAS28 calculated. Cytokines (IL1b, 10, 6. 5, 2, 4, 8, GMCS, TNFa, IFNg,) were determined using ELISA kit (Human ultrasensitive cytokine 10 -plex panel [Invitrogen, CA, USA]). GS and PD ultrasound was assessed in 7 joints according to Backhaus et al (2). Esaote MyLab ® 25 ultrasound machine with 12-18 MHz linear probe was used. <h3>Results</h3> 21 patients were included. Clinical and demographic data are shown in the table. GS synovitis was found in 95%, and tenosynovitis in 9.5%. PD was detected in 57%. There was no association between DAS28 and duration in clinical remission, disease duration and US-defined active synovitis (p=0.84, 0.309 and 0.762 respectively). Pro-inflammatory cytokines levels were elevated in patients with less than 6 months and in those with 13 to 24 months in clinical remission. Nevertheless, there was no correlation with US-defined synovitis (p=NS) <h3>Conclusions</h3> US detected a high percentage of subclinical synovitis in RA patients in clinical remission. Cytokine levels did not correlate with DAS 28 or ultrasound-defined active synovitis. <h3>References</h3> Brown AK, Conaghan P, Karim Z, et al. An explanation for the apparent dissociation between clinical remission and continues structural deterioration in rheumatoid arthritis. Arthritis Rheum 2008; 58(10): 2958-2967 Backhaus M, Ohrndorf S, Kellner H, et al. Evaluation of a novel 7-joint ultrasound score in daily rheumatologic practice: a pilot project. Arthritis Rheum 2009; 61(9): 1194-1201 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4855
CBIO-01COEXPRESSION OF FATTY ACID SYNTHASE (FASN) AND CARNITINE PALMITOYLTRANSFERASE 1C (CPT1C) IN HUMAN GLIOMAS
Authors: Tatsuya Abe, Tomihiro Wakamiya, Yukiko Nakahara, Satoshi O. Suzuki, Hiroyuki Honda, Masahiro Mizoguchi, Koji Yoshimoto, Toru Iwaki
Journal: Neuro-Oncology (2015)
FRI0131 Mannose binding lectin (MBL) deficiency is a major risk factor for multiple serious infections (SI) in rheumatoid arthritis
Authors: G. J. Carroll, K. Makin, B. Carroll, S. Curtin, M. Bulsara
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Infection is the leading cause of death in RA. Increasing age and use of corticosteroids (CS) are known risk factors (RF) for serious infection (SI). To what extent defects in the innate immune system (IIS) contribute to this risk is unknown. MBL, a component of the IIS is a liver protein with diverse functions including opsonisation and complement-mediated killing of various micro-organisms. <h3>Objectives</h3> The aim of this study was to determine whether MBL deficiency is a RF for multiple SIs in RA. <h3>Methods</h3> From 01/01/2007 to 30/01/2013, 207 RA patients derived from the clinics of a single Rheumatologist (private consulting rooms, rural and city hospital clinics) were evaluated to identify RFs for SI (infections requiring admission to hospital or IV antibiotics). MBL concentrations were mostly determined at the time of commencement of synthetic or biologic DMARD therapy. <h3>Results</h3> Patients with an MBL equal to or less than 56 ng/mL were found to be 4.2 times more likely to have at least one SI (OR =4.2, 95% CI 1.10 – 16.20, p = 0.036). Higher rates of SI were observed in recipients of biologic DMARDs (26.4%) compared to synthetic DMARDs (11.8%). Among recipients of biologic agents, SI rates (at least 1) were 3.7, 5.4 and 11.5 per 100 patient-years of treatment for those with normal MBL concentrations (&gt;1300 ng/ml), partial deficiency (&lt;1300 but &gt;56 ng / ml) and severe deficiency (&lt; 56 ng / ml) respectively. Multiple SIs were observed in 6 patients, 5 of whom had MBL concentrations &lt;56 ng / mL and all of whom had MBL concentrations &lt;400 ng / mL (OR = 51.8, 95% CI 5.6 – 474.9, P=0.0005). <h3>Conclusions</h3> MBL deficiency is a RF for SI in RA and especially multiple SIs. The risk for at least one SI is comparable to that of maintenance therapy with CS (dose = 5 mg or greater each day). Risk profiling, the development of serious infection risk calculators and the use of customised Action Plans for suspected infection may help to minimise the morbidity and mortality associated with sepsis in RA patients. <h3>Disclosure of Interest</h3> None Declared
First-in-human study of a novel nucleoside analogue, CP-4126, in patients with advanced solid tumors
Authors: B. Nilsson, A. Hendlisz, M. Castella, S. Aamdal, S. Dueland, M. Nyakas, J. Evans, B. Venugopal, W. Rasch, A. Awada
Journal: Journal of Clinical Oncology (2009)

2577 Background: CP-4126 (gemcitabine 5'-elaidic acid ester) is a novel nucleoside analogue with proven preclinical antitumor activity. Unlike gemcitabine, the intracellular uptake of CP-4126 is independent of nucleoside transporters. The aims of this study were to determine the safety, toxicity, MTD and the RD of CP-4126, to describe its pharmacokinetic (PK) characteristics, and to assess its preliminary antitumor activity. Methods: Patients (pts) with refractory solid tumors, performance status ECOG &lt; 2, with adequate haematologic, renal and hepatic function were enrolled in this dose escalation study (1–6 pts per dose level (DL)). CP-4126 was administered on days (d) 1, 8 and 15 every 4 week by a 30 min IV infusion. Start dose was 30 mg/m 2 /d and the dose was increased by 100% until toxicity &gt; CTCAE grade 2 occurred. Standard DLT definitions were used. Activity was assessed at the end of every 2 nd cycle (cy). Plasma and urine PK were determined during d1 (24 hrs) of cy1; plasma at all DLs and urine at DL= 1400 mg/m 2 /d. Results: 39 pts have been included, (m =24; f =15 ), median age 60 (range 19–78), receiving 96 cycles (range 1–9) of treatment, with 1 pt/DL from 30 to 240 mg/m 2 /d. The first grade 2 AE (neutropenia) was reported at 480 mg/m 2 /d. Most frequent toxicities include nausea, vomiting, fatigue and anorexia, the majority of mild severity (grade 1–2). 5 DLTs have been reported; 800 mg/m 2 /d (1 pt - d8 dose delay &gt;2 weeks due to grade 3 thrombocytopenia and anaemia); 1000 mg/m 2 /d (1 pt died 48 hrs after treatment start due to acute lung damage); 1400 mg/m 2 /d (1 pt - fatigue grade 3); 2 pts at 1600 mg/m 2 /d (grade 3 ALT/AST elevation [1 pt]; 1 pt grade 4 neutropenia and grade 3 fatigue). Stabilisation of disease (≥ 3 months) reported in 5 pts (pancreas, colon and ovarian cancer) lasting between 3.5 to 8 months. One ovarian pt had a 28.3% reduction in tumor mass. CP-4126 was detected in plasma up to 24 hrs post-dosing. AUC for dFdC exposure was significantly higher than reported with gemcitabine at comparable dose levels. Urinary excretion of the main metabolite dFdU during the first 24 hrs was approximately 60% of dose. Conclusions: CP-4126 is well tolerated and accrual is ongoing at 1400 mg/m 2 /d to establish RD for phase II studies. Updated results including plasma and urine PK will be presented. [Table: see text]
Anastomose gastro-jéjunale endoscopique par NOTES pure sur cochon vivant - Etude pilote
Authors: JM Gonzalez, S Berdah, G Vanbiervliet, T Bege, M Barthet
Journal: Endoscopy (2011)

Introduction: La NOTES se développe sur le plan diagnostique et thérapeutique depuis sa description en 2000. De nombreuses expérimentations sont couplées à une laparoscopie avec „single port„. Le but de notre étude était d'évaluer la faisabilité d'une anastomose gastrojéjunale par NOTES pure, perméable, fonctionnelle et étanche.
Utility of EUS to identify the effective responders from rectal cancer patients who receive neo-adjuvant chemotherapy
Authors: Zhang Xiaoyin, Guo Xuegang, Wang Xin, Du Jianjun, Zhao Qingchuan, Wu Kaichun, Fan Daimin
Journal: Endoscopy (2011)

Purpose: This study aimed to investigate if EUS can be chosen as an effective method to evaluate the treatment response and decide best time for operation of rectal cancer patients who receive neo-adjuvant chemotherapy.
GENERAL SEMANTICS
Authors: Douglas Gordon Campbell
Journal: American Journal of Psychiatry (1937)

The object of this paper is to call attention to the linguistic problems involved in contemporary psychiatry, not only in regard to psychiatric theory and nosology but in therapy as well. Linguistic factors are shown to be important determinants of personality structure, and cognizance of them is essential to any general theory of values upon which the rational treatment of personality deviation depends. Several contemporary leaders of psychiatric thought, among them William A. White, C. Macfie Campbell, Adolf Meyer and John T. MacCurdy, have mhde tentative generalizations and suggestions in this field, but it has remained for Alfred Korzybski to make a systematic investigation and evolve a general theory with specific application in psychiatric and other fields, thus relating many previously isolated areas of scientific knowledge into a synthetic "unified field theory" of what may be called general anthropology. The salient points of his work, as presented in his latest book, Science and Sanity,' are here presented with some discussion of their implications. In a later publication practical applications and clinical results will be reported.
Scoliosis and Fractures in Young Ballet Dancers
Authors: Michelle P. Warren, J. Brooks Gunn, Linda H. Hamilton, L. Fiske Warren, William G. Hamilton
Journal: New England Journal of Medicine (1986)

In a survey of 75 dancers (mean age, 24.3 years) in four professional ballet companies, we found that the prevalence of scoliosis was 24 percent and that it rose with increases in age at menarche. Fifteen of 18 dancers (83 percent) with scoliosis had had a delayed menarche (14 years or older), as compared with 31 of 57 dancers (54 percent) without scoliosis (P<0.04). The dancers with scoliosis had a slightly higher prevalence of secondary amenorrhea (44 percent vs. 31 percent), the mean (±SD) duration of their amenorrhea was longer (11.4±18.3 vs. 4.1±7.4 months; P<0.05), and they scored higher on a questionnaire that assessed anorectic behavior. The incidence of fractures was 61 percent (46 of 75 dancers), and it rose with increasing age at menarche. Sixtynine percent of the fractures that were described were stress fractures (mostly in the metatarsals), and their occurrence had an even stronger correlation with increased age at menarche. The incidence of secondary amenorrhea was twice as high among the dancers with stress fractures (P<0.01), and its duration was longer (P<0.05). In 7 of 10 dancers in whom endocrine studies were performed, the amenorrheic intervals were marked by prolonged hypoestrogenism. These data suggest that a delay in menarche and prolonged intervals of amenorrhea that reflect prolonged hypoestrogenism may predispose ballet dancers to scoliosis and stress fractures. (N Engl J Med 1986; 314:1348–53.)
BALLOON-EXPANDABLE TRANSCATHETER AORTIC VALVE REPLACEMENT IN PATIENTS WITH EXTREME AORTIC VALVE CALCIFICATION
Authors: Yigal Abramowitz, Hasan Jilaihawi, Tarun Chakravarty, Mohammad Kashif, Yoshio Maeno, Yoshio Kazuno, Nobuyuki Takahashi, Mamoo Nakamura, Wen Cheng, Raj Makkar
Journal: Journal of the American College of Cardiology (2015)
Drug efflux by breast cancer resistance protein (BCRP) is a mechanism of resistance to the insulin-like growth factor receptor/insulin receptor inhibitor, BMS-536924.
Authors: P Haluska, JM Carboni, YW Asmann, C Ten Eyck, RM Attar, JD Tibodeau, X Hou, T Nakanishi, DD Ross, SH Kaufmann, MM Gottardis, C Erlichman
Journal: Cancer Research (2009)

Abstract Abstract #2149 Background: Inhibitors of the insulin-like growth factor 1 receptor (IGF-1R) are currently undergoing clinical testing. Preclinical investigations have identified IGF-1 signaling as a key mechanism for breast cancer growth and resistance to clinically useful therapies, including tamoxifen and trastuzumab. Thus, agents targeting IGF-1R have promise in the treatment of breast cancer. Determining mechanisms that can confer resistance to these agents may aid their clinical development.&amp;#x2028; Methods: To understand factors may be important in predicting sensitivity to targeting the IGF-1 signaling pathway, we developed a cell line (MCF-7R4) that is resistant to BMS-554417, a small molecule, dual-kinase inhibitor of IGF-1R and insulin receptor (InsR). Compared with the parental MCF-7 cells, MCF-7R4 cells are 40- to 50-fold resistant to BMS-554417 and cross-resistant to the similar compound BMS-536924. The expression profiles of MCF-7R4 and that of MCF-7 were compared using Affymetrix GeneChip Human Genome U133 Plus 2.0 Arrays. Intracellular concentrations of BMS-536924 were examined by reverse phase high performance liquid chromatography. BMS-536924 cellular accumulation in vitro was visualized by fluorescence microscopy using a DAPI filter set. MCF-7 cells stably transfected with either the empty mammalian expression vector pcDNA (MCF-EV) or full length BCRP (MCF-BCRP) were examined for sensitivity to BMS 536924 by MTS assays.&amp;#x2028; Results: Compared to MCF-7 cells, BCRP expression was increased 9-fold in MCF-7R4, which was highly statistically significant by t-test (p= 7.13E-09). Little change was observed in other ABC transporter proteins, including ABCB1. No change was observed in IGF-1R or InsR expression. BCRP overexpression in MCF-7R4 cells was confirmed by western blotting. MCF-7R4 cells had significantly lower intracellular accumulation of BMS-536924 compared to MCF-7 cells. Confirming these results, MCF-BCRP cells were significantly less sensitive to the cytoxic effects of BMS-536924 cells than MCF-EV cells.&amp;#x2028; Conclusions: BCRP expression was stimulated by prolonged exposure of MCF-7 cells to BMS-554417. Upregulation of BCRP is one of the most significant changes observed in MCF-7R4 cells in comparison to parental cells. BCRP expression decreased cellular exposure to BMS-536924 and was sufficient to confer resistance. These data suggest that BSM-536924 is a substrate for BCRP-mediated efflux. Expression of BCRP may be important in de novo and acquired resistance to benzimidazole –based inhibitors of IGF-1R/InsR. Supported in part by the Mayo Clinic Breast SPORE (CA116201-03), NIH K12 (CA090628-05) and the Mayo Clinic Cancer Center (CA15083). Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2149.
1272 DECREASED SERUM LEVELS OF FIBROBLAST GROWTH FACTORS 19 AND 21 CORRELATE WITH SEVERITY OF TISSUE DAMAGE IN PEDIATRIC NAFLD
Authors: A. Alisi, N. Panera, S. Ceccarelli, C. Della Corte, D. Comparcola, M. Sartorelli, A. Alterio, S. Petrini, A. Feldstein, V. Nobili
Journal: Journal of Hepatology (2012)
Positive Leukocyte and Negative Bone Scintigraphy in Extensive Arthroplasty Infection
Authors: Tack Shin Lee, Robert Elliott, Kevin Allman, Hans Van Der Wall
Journal: Clinical Nuclear Medicine (2003)

An 85-year-old male resident of a nursing home presented after a fall with a painful left hip, confusion, and fever. He had multiple medical problems including severe vascular disease and poor vision as a result of macular degeneration. An Austin Moore left hip prosthesis had been inserted for a fractured femoral neck several years before. A septic workup showed a raised leukocyte count but no other focal abnormality. Plain radiography showed a periprosthetic fracture of the left hip. Blood cultures grew beta-hemolytic group A Streptococcus sensitive to penicillin. Bone scintigraphy was thought to be consistent with loosening of the prosthesis without evidence of a recent fracture. Tc-99m leukocyte scintigraphy was markedly abnormal, with extensive soft-tissue uptake suggestive of a large periprosthetic infective collection. This was confirmed at surgery with drainage of 200 mL pus from the left hip, and deep and superficial soft tissues of the thigh. The trochanteric fracture was well granulated and thought to be of long standing. The prosthesis was removed and the patient was treated with appropriate antibiotics with good effect.
Advocacy Group Update: Setting the Cancer Agenda
Authors: L. Fintor
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Advocacy Group Update: Setting the Cancer Agenda Get access Lou Fintor Lou Fintor Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 8, 21 April 1993, Pages 607–608, https://doi.org/10.1093/jnci/85.8.607 Published: 21 April 1993
METABOLOMIC PROFILING IN HEART FAILURE IDENTIFIES BIOMARKERS OF MITOCHONDRIAL FUNCTION IN PRESERVED VERSUS REDUCED EJECTION FRACTION
Authors: Wynn Hunter, Jacob Kelly, Damian Craig, Carol Haynes, Robert McGarrah, Eric Velazquez, G. Michael Felker, Adrian Hernandez, Olga Ilkayeva, Robert D. Stevens, James Bain, Michael Muehlbauer, Christopher Newgard, William Kraus, Svati Shah
Journal: Journal of the American College of Cardiology (2015)