tbuckley/cabot-search huggingface dataset:
Abstract 1192: Impedance based kinetic cellular response profiling in drug discovery and development
Authors: Ning Ke, Xiaobo Wang, Xiao Xu, Yama Abassi
Journal: Cancer Research (2010)

Abstract A novel cell-based kinetic profiling approach using impedance readout for monitoring the effect of small molecule compounds will be described. This non-invasive readout allows continuous sampling of cellular responses to biologically active compounds and the ensuing kinetic profile provides information regarding the temporal interaction of compounds with cells. The utility of this approach was tested in two approaches. First, compounds with similar mechanism of action produced similar impedance-based time-dependent cell response profiles (TCRP). The TCRP was used to identify novel mechanisms for existing drugs and also identified potential off-target activity for COX-2 inhibitor, celecoxib and the experimental compound, monastrol. The second approach entailed using this profiling approach to screen a 120,000 compound library. We identified novel anti-mitotic compounds as well as compounds interfering with DNA synthesis. Furthermore, we also identified compounds specific for oncogene addiction pathways. We will present data in support of both approaches in this presentation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1192.
Abstract 817: KRAS and BRAF mutation spectrum in 1,035 FFPE tumor samples submitted for clinical testing
Authors: Ryan P. Bender, Matthew J. McGinniss, Liza Dejesa-Jamanila, Christine Kuslich
Journal: Cancer Research (2010)

Abstract Activating mutations in both the KRAS and BRAF genes are associated with poor prognosis and non-response to anti-EGFR therapies in patients with advanced cancers. Clinical guidelines have recommended that KRAS mutational status be determined in all patients with metastatic colorectal cancer that are being considered for anti-EGFR therapies. In this study, a pathologist reviewed an H&amp;E slide of each tumor sample and determined the percent tumor nuclei and percent necrosis. Each specimen was macrodissected and DNA was extracted. DNA was then amplified with primers flanking KRAS exon 2 (codons 12 and 13), and KRAS exon 3 (codon 61), and BRAF exon 15. Using the ABI3730 and Mutation Surveyor software, mutations were scored as positive when evident in both the forward and reverse reactions. Following analysis of the 1,035 clinical tumor specimens submitted to our lab for KRAS mutation analysis by direct sequencing, 387 or 37% had a mutation. Codon 61 mutations accounted for 18 of the 387 mutations identified, or 4.6%. Furthermore, four rare KRAS mutations were identified [G12dup, G12L, G13R and G13C]. These 22 mutations would not be detected by the commonly used clinical qPCR KRAS mutational analysis kits, as they are designed to identify only the 7 most common codon 12 and 13 mutations. Colorectal specimens accounted for 684 of the 1,035 samples in the study of which 286 or 41% of these had KRAS mutations. Of the 237 clinical specimens tested for BRAF exon 15 mutations, 28 or 12% had mutations. Of these, 26 were the common V600E mutation, but two were rare [c.1798_1799GT&amp;gt;AA (p.V600K) and c.1798_1799GT&amp;gt;AG (p.V600R)]. Both of the rare mutations were present in skin cancer samples. Colon specimens had a BRAF mutation rate of 10%, while skin specimens had a mutation rate of 61%. Mutational analysis of KRAS in tumor samples by direct DNA sequencing detects a greater variety of mutations in KRAS than kit-based qPCR assays, including mutations that affect codon 61. Based on the data presented omitting rare variants in codons 12 and 13 and omitting codon 61 would decrease the analytical sensitivity of KRAS mutational analysis to 94%. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 817.
COMPARABLE 2-YEAR PATENCY RATE FOLLOWING SUBINTIMAL AND INTRALUMINAL DRUG-ELUTING STENT IMPLANTATION FOR FEMOROPOPLITEAL CHRONIC TOTAL OCCLUSION
Authors: Takayuki Ishihara, Mitsuyoshi Takahara, Osamu Iida, Yoshimitsu Soga, Keisuke Hirano, Yasutaka Yamauchi, Kan Zen, Daizo Kawasaki, Shinsuke Nanto, Hiroyoshi Yokoi, Masaaki Uematsu
Journal: Journal of the American College of Cardiology (2016)
P216 Local Endobronchial Ultrasound (ebus) Service Reduces Waiting Time For Test Results
Authors: J. Dickson, M. Lawson
Journal: Thorax (2014)

<h3>Introduction</h3> Endobronchial ultrasound (EBUS) is increasingly used in investigating mediastinal lymphadenopathy. A recent Thorax paper suggested EBUS should only be performed in large centres to ensure quality. A recently established EBUS service at Broomfield Hospital appeared to reduce the time taken to obtain results compared to the regional service previously used. The service was audited to ensure quality and evaluate changes to pathway times. <h3>Objectives</h3> Compare time from decision for EBUS to test result between local and regional service and ensure safety and accuracy. <h3>Methods</h3> Data were collected prospectively for all EBUS cases after the local service was established in August 2013. Accuracy and safety of the service were audited based on the first 8.5 months of operation. Data were extracted from the MDT database for patients referred to the regional service between November 2013 and January 2014. Time from MDT decision for EBUS referral and subsequent MDT discussion of results were compared between both services. Data were compared using the Mann-Whitney U test using the statistics package in R. <h3>Results</h3> Average time from decision to EBUS result was 19 days in the local service based on the first 21 cases performed. There was a 40 day average turnaround for the regional service based on the 10 cases referred between November 2013 and January 2014. This represented a statistically significant reduction in waiting time of 21 days (p = 0.0001). The local service was safe and accurate with no reported complications in 42 cases over the first 8.5 months and an overall accuracy of 88% increasing to 94% (31/33) in suspected cancer cases. <h3>Conclusions</h3> Our recently established local EBUS service is safe and accurate but also significantly reduces the time between decision to EBUS and test results discussed in MDT compared to the regional referral service previously used. This is important for patients on the 62-day cancer pathway. A local service enables people to undergo investigations nearer to home. The establishment of national reference standards for EBUS is important to ensure optimal quality but this can be achieved in local services which may offer additional benefits to patients.
Risk of Malignant Mixed Mullerian Tumors After Tamoxifen Therapy for Breast Cancer
Authors: Rochelle E Curtis, D Michal Freedman, Mark E Sherman, Joseph F Fraumeni
Journal: JNCI Journal of the National Cancer Institute (2004)

Recent studies have indicated that the tamoxifen-related risk of uterine corpus cancer may be especially high for some uncommon cell types, although the magnitude of risk has not been quantified. We evaluated data from 39 451 breast cancer patients diagnosed from 1980 through 2000 who were initially treated with tamoxifen and found that the overall risk of subsequent uterine corpus cancer was increased more than twofold (observed-to-expected ratio [O/E] = 2.17, 95% confidence interval [CI] = 1.95 to 2.41) relative to the general SEER population. The relative risk was substantially higher for malignant mixed mullerian tumors (MMMTs) (O/E = 4.62, O = 34, 95% CI = 3.20 to 6.46) than for endometrial adenocarcinomas (O/E = 2.07, O = 306, 95% CI = 1.85 to 2.32), although the excess absolute risk was smaller—an additional 1.4 versus 8.4 cancers per 10 000 women per year, respectively. Among those who survived for 5 years or longer, there was an eightfold relative risk for MMMTs and a 2.3-fold risk for endometrial adenocarcinomas, with patients developing MMMTs having a worse prognosis. These findings indicate that tamoxifen may have delayed effects, such as the increased risk of MMMTs, rare but aggressive tumors of unclear pathogenesis.
PTU-040 Alcohol: always detrimental to the immune system? The role of active alcohol consumption on neutrophil function in alcohol-related cirrhosis
Authors: J M Ryan, N J Taylor, G K Manakkat Vijay, T H Tranah, R D Abeles, A Riva, N Vergis, L Markwick, S Chokshi, J O'Grady, J A Wendon, Y Ma, D L Shawcross
Journal: Gut (2012)

<h3>Introduction</h3> Neutrophil dysfunction has been reported in patients with alcohol-related cirrhosis (ARC) and is associated with increased risk of infection and mortality. There is a paucity of understanding regarding the mechanisms of immune dysfunction in patients with active alcohol consumption and ARC. This study aimed to characterise neutrophil phenotype, functionality and plasma cytokine profiles in abstinent patients with ARC (n=17) compared to those actively drinking (n=19), split by MELD score &lt;15 vs &gt;15 compared to healthy controls (n=12). <h3>Methods</h3> Neutrophils were isolated from patients with ARC. Phagocytic capacity was analysed by flow cytometry using FITC-labelled <i>Escherichia coli</i> and oxidative burst (OB) was determined by the percentage of neutrophils producing reactive oxygen species (ROS) at rest, and after stimulation with opsonised <i>E Coli</i>. Neutrophils were stained with anti-CD11b (APC-Cy7), -CD16 (PE) and –TLR4 (biotin-conjugated PE-Cy7 Streptavidin). Plasma cytokine profiling was performed using cytokine bead array. <h3>Results</h3> Phagocytosis was significantly reduced in the cirrhotic groups compared to controls (p=0.02) however this was not influenced by MELD score or abstinence. Spontaneous OB was significantly increased in the cirrhotic groups compared to controls (p=0.03). Median spontaneous OB in the abstinent patients with MELD &lt;15 was 26% [IQR 8–42] compared to 10% (IQR 7–44) in those actively drinking. Median spontaneous OB in the abstinent group with MELD&gt;15 was 31% (IQR 8–61) compared to 14% (IQR 4–29) in the active alcohol-drinkers. Stimulated burst was not impaired in the cirrhotic groups, with comparative values to controls. Plasma pro- and anti-inflammatory cytokine profiles were not discriminatory between the groups. Baseline TLR4 expression was increased in the MELD&gt;15 abstinent group compared to active drinkers (p=0.004); alcohol attenuated resting TLR4 expression to values seen in controls. <h3>Conclusion</h3> Active alcohol consumption did not impact on neutrophil phagocytic capacity but reduced spontaneous OB by 50% with a reduction in the generation of ROS and decreased resting TLR4 expression. This supports a paradoxical anti-oxidant role of active alcohol drinking in patients with ARC that may promote endotoxin tolerance and warrants further investigation. <h3>Competing interests</h3> None declared.
Human Determinants and the Role of Melanocortin-1 Receptor Variants in Melanoma Risk Independent of UV Radiation Exposure
Authors: Judith Wendt, Sabine Rauscher, Sebastian Burgstaller-Muehlbacher, Ingrid Fae, Gottfried Fischer, Hubert Pehamberger, Ichiro Okamoto
Journal: JAMA Dermatology (2016)

<h3>Importance</h3> Despite the unquestioned relationship of UV radiation (UVR) exposure and melanoma development, UVR-independent development of melanoma has only recently been described in mice. These findings in mice highlight the importance of the genetic background of the host and could be relevant for preventive measures in humans. <h3>Objective</h3> To study the role of the melanocortin-1 receptor (<i>MC1R</i>) and melanoma risk independently from UVR in a clinical setting. <h3>Design, Setting, and Participants</h3> Hospital-based case-control study, including genetic testing, questionnaires, and physical data (Molecular Markers of Melanoma Study data set) including 991 melanoma patients (cases) and 800 controls. <h3>Main Outcomes and Measures</h3> Association of<i>MC1R</i>variants and melanoma risk independent from sun exposure variables. <h3>Results</h3> The 1791 participants included 991 with a diagnosis of melanoma and 800 control patients (mean [SD] age, 59.2 [15.6] years; 50.5% male). Compared with wild-type carriers, carriers of<i>MC1R</i>variants were at higher melanoma risk after statistically adjusting for previous UVR exposure (represented by prior sunburns and signs of actinic skin damage identified by dermatologists), age, and sex compared with wild-type carriers (≥2 variants, OR, 2.13 [95% CI, 1.66-2.75],<i>P</i> &lt; .001;<i>P</i>for trend &lt;.001). After adjustment for sex, age, sunburns in the past, and signs of actinic skin damage, the associations remained significant (OR, 1.65 [95% CI, 1.02-2.67] for R/R, OR, 2.63 [95% CI, 1.82-3.81] for R/r; OR, 1.83 [95% CI, 1.36-2.48] for R/0; and OR, 1.50 [95% CI, 1.01-2.21] for r/r, with<i>P</i>values ranging from &lt;.001 to .04 when adjusted for facial actinic skin damage; OR, 2.36 [95% CI, 1.62-3.43] for R/r; and OR, 1.47 [95% CI, 1.08-1.99] for R/0 with<i>P</i>values ranging from &lt;.001 to .01 when adjusted for dorsal actinic skin damage; and OR, 2.54 [95% CI, 1.76-3.67] for R/r, OR, 1.75 [95% CI, 1.30-2.36] for R/0; and OR, 1.50 [95% CI, 1.02-2.20] for r/r with<i>P</i>values ranging from &lt;.001 to .04 when adjusted for actinic skin damage on the hands). <h3>Conclusions and Relevance</h3> Carriers of<i>MC1R</i>variants were at increased melanoma risk independent of their sun exposure. Further studies are required to elucidate the causes of melanoma development in these individuals.
849 INTERPLAY BETWEEN BASIC RESIDUES OF HEPATITIS C VIRUS GLYCOPROTEIN E2 WITH LIPOPROTEINS, VIRAL RECEPTORS AND NEUTRALIZING ANTIBODIES
Authors: G. Koutsoudakis, J. Dragun, S. Perez del Pulgar, M. Coto-Llerena, L. Mensa, G. Crespo, M. Navasa, X. Forns
Journal: Journal of Hepatology (2012)
Cultured Mouse Mammary Epithelial Cells: Normal Phenotype After Implantation&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: U K Ehmann, R C Guzman, R C Osborn, J T Young, R D Cardiff, S Nandi
Journal: JNCI Journal of the National Cancer Institute (1987)

Mammary epithelial cells from normal virgin BALB/c mice were cultivated in vitro by the feeder cell technique developed and reported previously. These cells were cultured up to the 10th passage, equivalent to 60 cell divisions in culture. They were then tested for normality by several criteria, namely, the ability to regrow into normal mammary glands after implantation into cleared mammary fat pads of both syngeneic and nude mice, chromosome numbers, and response to mammogenic hormones. The cultured cells did form normal mammary ducts after implantation. The fraction of fat pads with ductal outgrowths as well as the size of the outgrowths was proportional to the number of cells implanted. When 106 cells were implanted into BALB/c mice, 83% of the fat pads contained outgrowths, filling, on the average, approximately 87% of the fat pad. More ductal outgrowths occurred from implanted cells taken from lower tissue culture passages than from high ones, and the number of outgrowths was greater in BALB/c mice than in nude mice. A small fraction of the cells in culture reacted with antibodies to casein, but there was no evidence of α-lactalbumin in the cells. However, ductal outgrowths from implanted cells responded to hormone stimulation of an estrogen deoxycorticosteroid pellet by forming well-developed lobulo-alveolar structures characteristic of pregnancy. Of the cells that were studied in passages 3 and 7, 85% were diploid. An abnormally growing culture in passage 10 was composed of cells in the tetraploid range. These tetraploid cells formed normal mammary ducts when implanted into animals.
FDG PET Differentiation of Tumor Recurrence From Post-Stereotactic Radiosurgical Scar in a Central Neurocytoma
Authors: Yiyan Liu
Journal: Clinical Nuclear Medicine (2013)

Central neurocytoma is a rare benign tumor of neuronal origin. The tumor is often located in the ventricular system and can proliferate within the ventricle. Five months after stereotactic radiosurgery for recurrent neurocytoma, a 33-year-old woman had a 2.0-cm lesion in the right third ventricle on the MRI. FDG PET demonstrated intense uptake of the lesion. The subsequent MRI follow-up showed growth of the lesion and confirmed recurrence.
Hypertriglyceridemia Associated with Deficiency of Apolipoprotein C-II
Authors: W. Carl Breckenridge, J. Alick Little, George Steiner, Anne Chow, Mary Poapst
Journal: New England Journal of Medicine (1978)

A 59-year-old man with severe hypertriglyceridemia and no post-heparin lipolytic activity was studied because of a marked fall in plasma triglyceride concentrations after a blood transfusion. An apolipoprotein activator (apolipoprotein C-II) for lipoprotein lipase could not be detected by polyacrylamide-gel electrophoresis of apoproteins, immunodiffusion of the plasma against anti-apolipoprotein C-II or activation assays for lipoprotein lipase. Furthermore, the patient's triglyceride-rich lipoproteins would not serve as substrate for lipoprotein lipase. The patient had latent post-heparin lipolytic activity, which appeared after the addition of apolipoprotein C-II to the post-heparin plasma. After a transfusion of 1 unit of plasma from a normal subject the patient's plasma triglycerides fell, within one day, from 1000 to 250 mg per deciliter and remained below preinfusion concentrations for six days. We conclude that this patient's hyperlipoproteinemia resulted from a deficiency of apolipoprotein C-II. (N Engl J Med 298:1265–1273, 1978)
SP0117 How to Optimize Doppler Settings for Slow Flow
Authors: L. Terslev
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Doppler ultrasound allows the visualization of perfusion in the inflamed synovium and therefore allows the diagnosis and quantification of inflammatory activity in a joint, tendon or enthesis. The issue when choosing Doppler modality in a rheumatological setting is the sensitivity for slow flow. This may be colour of power Doppler depending on the machine. Always choose the Doppler modality that provides the most flow information. The preset on the ultrasound machines are not per se set optimally for slow flow. The most important parameters to adjust are frequency, gain, PRF and thereby the filters, focus and colour priority. <i>Doppler frequency</i> behaves as the grey-scale frequency. High Doppler frequency gives better resolution on the expense of penetration. <i>Gain</i> determines the sensitivity of the system to slow flow and is adjusted by increasing the gain until noise pixels are present in the image and then gradually lowering the gain until only very few noise pixels are seen in the image. By lowering the gain further noise and motion artefacts may be prevented but also loss of slow flow information. The <i>PRF i</i>s the pulse repetition frequency and determines the sensitivity to slow flow. The PRF must be kept as low as possible (around 500 Hz) because linked with the PRF adjustments are the filters. The higher the PRF the higher the filters are and high filters will eliminate slow flow. <i>Focus</i> in Doppler is like focus in grey-scale. It must be palce in the region of interest to get optimal resolution. <i>Colour priority</i> may not be adjusted easily in all machine but is a function that determines what is the most important in the image: the colours or the greys. Also adjust to a 100% to ensure maximal flow information. Adjusting the many parameters of the Doppler should not be done at every examination. Fortunately, there is little difference from patient to patient and from joint to joint with respect to Doppler settings. An exception is the hip joint because of its deep location. Once the sensitivity of the Doppler has been maximised, the settings may be saved as a set-up, which the machine reverts to at every new exam. It is possible to have many different set-ups, which can be named to our liking such as knee, obese knee, wrist etc. Using the same settings from patient to patient and from visit to visit is important if we wish to gauge the treatment response longitudinally or compare patients. Therefore it is also important that the same make and model of ultrasound machine are used from visit to visit. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6258
Abstract 2621: Relative excess risk due to interactions between GWAS-identified susceptibility loci and other breast cancer risk factors
Authors: Amit D. Joshi, Anika Hüsing, Daniele Campa, Federico Canzian, Tyler J. VanderWeele, Peter Kraft
Journal: Cancer Research (2012)

Abstract Background: The characterization of the joint effects of multiple susceptibility loci identified in genome wide association studies (GWAS) and known breast cancer risk factors has the potential to inform functional mechanisms of carcinogenesis, public health guidelines and disease risk prediction. Additive interactions- departures from additivity on the absolute risk scale- can have public health and etiologic implications, but are infrequently reported. Methods: We assessed additive interactions among 11,043 non Hispanic White breast cancer cases and 11,665 similar controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Logistic regression models were used to calculate estimates and confidence intervals for risk excess due to interactions (RERI) between 34 GWAS identified breast cancer susceptibility SNPs and 10 established breast cancer risk factors (age at menarche, parity, age at first full term pregnancy, age at menopause, family history, Gail score, height, body mass index (BMI), alcohol consumption and smoking status). All analyses were adjusted for age (5 year intervals) and cohort. Results and conclusions: After correction for multiple comparisons, we identified a statistically significant RERI (estimate = 0.48, CI=0.24,0.72, uncorrected p-value = 0.0000877) between a SNP in RAD51L1 gene, rs10483813, and BMI (&amp;lt;30 vs. &amp;gt;=30 kg/ m2). Among non-carriers of the risk allele, high BMI was found to significantly protect against breast cancer, but no difference in risks was observed due to BMI among carriers of at least one risk allele. This intriguing result requires replication. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2621. doi:1538-7445.AM2012-2621