tbuckley/cabot-search huggingface dataset:
Abstract 4877: High throughput proteomic applications using protein A/G magnetic beads
Authors: Joanna Doyle, Matthew Ray, Anlong Ouyang, Betsy Benton, Peter A. Bell
Journal: Cancer Research (2011)

Abstract Speed and sample purity are key issues for proteomics researchers. Sample and data-processing throughputs are current bottlenecks in proteomic analysis. Magnetic separations can provide greater consistency and automation of proteomic sample preparation. We report here the development of a novel 1µm protein A/G magnetic bead that enables fast and convenient isolation of proteins via immunoenrichment. Thermo Scientific Pierce Protein A/G Magnetic Beads use a recombinant protein A/G that combines the IgG binding domains of both protein A and protein G. Protein A/G contains four Fc-binding domains from protein A and two from protein G, making it a convenient tool for capture of immunoglobulins from a variety of species and isotypes. Recombinant protein A/G was covalently coupled to 1 μm, blocked double-shelled magnetic particles with a polymeric core. The beads had a binding capacity of &amp;gt;60 μg rabbit IgG per mg bead along with low non-specific binding. Using a Thermo Scientific KingFisher Flex Magnetic Particle Processor, antibodies were purified from serum or ascites with high yield using the Pierce Protein A/G Magnetic Beads. The beads were also used to immunoprecipitate and co-immunoprecipitate multiple proteins significant to different phases of the cell cycle, including cyclin B, Cdk1, cyclin E, and cyclin D. U2OS and HeLa cell lines were first synchronized in serum starved media. The media was replaced with enriched media and cells were harvested at 4 hours (beginning of G1 phase), 6 hours (end of G1 phase), and 18 hours (end of G2 phase). Proteins were effectively isolated from the cell lysates using Pierce Protein A/G Magnetic Beads and identified by Western blot. In addition, these beads were successfully used in a chromatin-immunoprecipitation (ChIP) assay to measure binding of RNA Polymerase II to the proximal myc promoter in A431 lung carcinoma cells treated with and without EGF. In Conclusion, the results indicate that Pierce Protein A/G Magnetic Beads can effectively isolate protein targets in a variety of proteomic applications. 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 4877. doi:10.1158/1538-7445.AM2011-4877
458 N-GLYCOSYLATION MUTATIONS WITHIN HBSAG MAJOR HYDROPHILIC REGION CONTRIBUTE MOSTLY TO HEPATITIS B VIRUS IMMUNE ESCAPE MUTANT THROUGH ENHANCING VIRAL FITNESS
Authors: D. Yu, X. Li, V. Mom, X.-W. Liao, Y. Han, C. Pichoud, Q. Gong, D. Hua, P. Deny, F. Zoulim, X. Zhang
Journal: Journal of Hepatology (2012)
Phase II study of total therapy 3 (TT3) with added bortezomib (V) for multiple myeloma (MM)
Authors: B. Barlogie, E. Anaissie, J. D. Shaughnessy, F. van Rhee, K. Hollmig, M. Pineda-Roman, A. Mohiuddin, M. Zangari, G. Tricot, J. Crowley
Journal: Journal of Clinical Oncology (2007)

8020 Background: Building on the success of TT2 with OS exceeding a median of 8 yr, TT3 incorporated V into induction and consolidation/maintenance of melphalan (MEL)-based tandem transplants. Methods: Newly diagnosed patients with MM up to age 75 yr (&gt;59 yr, 47%) were enrolled in TT3, consisting of 2 cycles of V, thalidomide, dexamethasone, cisplatin, adriamycin, cyclophosphamide, etoposide (VTD-PACE) as induction prior to and as consolidation after MEL transplants, followed by maintenance with monthly VTD in year 1 and TD in years 2 and 3. The primary endpoint was complete response (CR). Results: 303 eligible patients were accrued between 02/04 and 07/06; median follow-up is 19 mo. Tandem transplants were completed in 84% with TT3 and 66% with TT2 (p&lt;0.0001) with similar 12-mo TRM (4% v 5%). At 24 mo, 84% v 68% achieved n-CR including 59% v 44% CR (both p&lt;0.0001). 24-mo EFS is superior (83% v 75%, p=0.02; &lt;65 yr: 86% v 76%, p=0.008) while 24-mo OS is still similar (86% v 85%, p=0.44; &lt;65 yr: 88% v 85%, p=0.16). In gene array-based high-risk MM, 24-mo EFS was 62% v 27% (p=0.006) and 24-mo OS was 74% v 43% (p=0.06). Independent adverse parameters for OS with TT3 were LDH&gt;=190 U/L (27%; HR=3.78, p=0.002), high-risk gene array (14%; HR=3.30, p=0.006) and age &gt;=65 yr (29%; HR=2.23, p=0.044). Compared to the T arm of TT2, fewer patients in TT3 experienced grade &gt;2 tremor (3% v 13%, p&lt;0.001), constipation (6% v 14%, p=0.002), syncope (1% v 12%, p&lt;0.001) and thrombo-embolic events (27% v 38%, p=0.004). Conclusion: Compared to TT2, added V and shortened induction in TT3 increased tandem transplant compliance, effected higher CR and n-CR rates and extended EFS with a strong trend for superior OS in high-risk MM in patients &lt;65 yr. TT3 toxicity was reduced in comparison with the T arm of TT2. No significant financial relationships to disclose.
Abstract SY02-01: Regulators of in situ to invasive breast carcinoma progression.
Authors: Kornelia Polyak
Journal: Cancer Research (2013)

Abstract A major clinical diagnostic criterion that differentiates in situ from invasive breast carcinoma is the presence of a continuous myoepithelial cell layer and basement membrane. In pre-invasive lesions such as DCIS, a relatively intact myoepithelial cell layer and basement membrane are still observed, but we have found that the molecular profiles of DCIS-associated myoepithelial cells are distinct from those from normal breast. The mechanisms underlying the loss of myoepithelial cells during the in situ to invasive breast carcinoma transition are unknown. We hypothesized that the differentiation of breast epithelial progenitors into myoepithelial cells is progressively inhibited by signals from tumor epithelial cells and cells composing the microenvironment such as fibroblasts and leukocytes. As a consequence, the myoepithelial cell layer is progressively lost and eventually disappears resulting in progression to invasion. We have been testing this hypothesis by characterizing myoepithelial cells from normal human breast tissues from nulliparous and parous women, including BRCA1 and BRCA2 mutation carriers. To dissect the functional properties of different types of myoepithelial cells, we have been using the MCFDCIS xenograft model. Our results will not only improve the current understanding of the role of myoepithelial cells but also have the potential to provide new prognostic markers to predict risk of invasive progression in DCIS. Furthermore, our results may help identify new targets for chemoprevention aimed at decreasing the risk of invasive breast tumors. Citation Format: Kornelia Polyak. Regulators of in situ to invasive breast carcinoma progression. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr SY02-01. doi:10.1158/1538-7445.AM2013-SY02-01
Blockade of Notch Signaling with Gamma-Secretase Inhibitors Induces Apoptosis in the Stem-Like Population of Breast Cancer Cells.
Authors: K. Foreman, P. Grudzien, S. Lo, P. Robinson, K. Albain, P. Strack, L. Miele
Journal: Cancer Research (2009)

Abstract BACKGROUND: Numerous studies have identified stem-like cells, termed cancer stem cells (CSCs), in breast tumors and established cell lines. These self-renewing CSCs are believed to be responsible for breast cancer formation, progression and recurrence; therefore, a deeper understanding of the signaling pathways regulating their survival will benefit development of novel therapeutic strategies. Notch signaling, which is known to be dysregulated in breast cancer and has been implicated in mammary stem cell self-renewal, can be effectively blocked by gamma-secretase inhibitors (GSIs). While GSIs are currently in clinical trials for breast cancer, it is unclear how these compounds will affect CSCs or if CSCs from different breast cancer phenotypes (estrogen receptor-alpha (ER)-positive, ER negative, Her2/neu overexpressing) will be differentially affected. We previously reported that stem-like cells derived from the T47D breast cancer cell line showed elevated levels of Notch activity and Notch inhibition using GSIs or Notch decoy proteins abolished secondary mammosphere formation.METHODS: We have expanded our studies to breast cancer cell lines of different phenotypes (T47D-A18, T47D-C42, MCF7, SKBR3, BT474, MBA-MD231) and five primary clinical specimens. We studied expression of a panel of Notch pathway genes including Notch receptors, ligands and immediate downstream targets of Notch activation in CSCs and non-CSCs. We also determined the effect of Notch inhibition on secondary mammosphere formation (a measure of self-renewal) and clonogenicity. We evaluated cell death using TUNEL assays.RESULTS: We report that CSCs possess elevated levels of Notch activation compared to non-CSCs regardless of breast cancer phenotype or sample origin (cell culture or primary tumor). However, the specific Notch target genes most abundantly expressed vary depending on the cell line, and may suggest that CSC from different subtypes of breast cancer have different “Notch signatures”. Blockade of Notch signaling with a GSI abolished secondary mammosphere formation, eventually resulting in apoptosis, a finding that was consistent for ER-positive, ER-negative, and Her2/neu overexpressing cancer cells and primary tumor samples from heavily pre-treated, late-stage patients. Furthermore, GSIs blocked colony formation in soft agar.CONCLUSIONS: These novel findings support a role for Notch signaling in CSC self-renewal and proliferation, and they suggest Notch inhibition with agents currently in clinical development may prove beneficial in targeting CSCs in a wide variety of breast cancers. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1154.
IMPACT OF MASKED HYPERTENSION ON SILENT CEREBRAL ISCHEMIA EVALUATED USING 24-HOUR AMBULATORY BLOOD PRESSURE MONITOR AND MAGNETIC RESONANCE IMAGE
Authors: Yong-Hyun Kim, Seong-Hwan Kim, Jin-Seok Kim, Hyung-Suk Seo, Chol Shin, Seung-Ku Lee, Hong-Euy Lim
Journal: Journal of the American College of Cardiology (2015)
AB1086 Pathological fracture revealing severe tabetic arthropathy
Authors: K. Berrada, H. Hachimi, L. Tahiri, L. Benchat, F.Z. Mernissi, T. Harzy
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Tabetic arthropathy is a devastating complication of neuro-syphilis, now becoming scarce due to early treatment of syphilis.The articular involvement may concern every joint, but more particularly concerns those of the lower limbs. <h3>Methods</h3> We report a new case of tabetic arthropathy revealed by pathological fracture. <h3>Results</h3> A 43-year-old man with a history of genital ulcer 20 years earlier presented with progressive painless swelling of the right knee lasting for four years. Two months before his admission, he suffered from a functional disability following a small trauma.The clinical examination revealed an important painless non-inflammatory hydarthrosis of the right knee, genu varum deformity, ligamentous laxity, and bilateral patellar hyporeflexia. Knee radiographs showed a hypertrophic arthropathy with fracture-dislocation of the distal femur, a massive joint destruction, fragmentation, bone sclerosis, and enormous osteophytosis formation. The syphilitic serology was positive in blood, cerebrospinal fluid (CSF) and synovial fluid. A treatment by G-penicillin was introduced. Surgical treatment was not possible because of the important osteoarticular destructions. <h3>Conclusions</h3> Our case illustrates the difficulty in therapeutic management of tabetic arthropathy which is a severe disease responsible of functional disability affecting quality of life. The best treatment is prevention based on the detection and treatment of syphilis at an early stage before the occurrence of joint and neurological complications. <h3>Disclosure of Interest</h3> None Declared
Probiotics and antibiotic associated diarrhoea
Authors: M. Battle
Journal: BMJ (2002)

Editor—D'Souza et al evaluated potential agents for the prevention of antibiotic associated diarrhoea, whose full spectrum of activity is immense both in the community and in hospital.1 In particular, the antitherapeutic default selection of Clostridium difficile with resultant colitis is associated with a considerable morbidity and mortality.
P165 Non-tuberculosis mycobacterium infection in Cystic Fibrosis lung disease; effects on bacterial community
Authors: R. Sattar
Journal: Thorax (2011)

<h3>Background</h3> Species of Non-Tuberculosis Mycobacterium (NTM), mainly <i>Mycobacterium abscessus</i> (<i>M abscessus</i>) is of increasing concern in Cystic Fibrosis (CF). <i>M abscessus</i> are present in the CF lungs as part of the complex microbiological community. The mode of growth of <i>M abscessus</i> in vitro is in biofilms; this maybe a contributing factor for the resistance to antimicrobial agents. Lung infections with <i>M abscessus</i> is a major concern in CF patients, as it is difficult to treat them. It has been described that, fatal infections are likely to occur after lung transplantations; therefore pre-transplant colonisation with <i>M abscessus</i> has become a relative contraindication to lung transplantation. NTM are recognised pathogens in the CF airways, but associations with clinical outcomes still remains unclear. <h3>Objectives</h3> The aim of the present study was to determine whether adult CF patients with pulmonary NTM infection have worse clinical outcomes, when compared to a matched group of CF patients who have never had NTM isolated. Additionally, the study also aims to determine what proportion of the overall bacterial community is NTM compared to other bacteria. <h3>Method</h3> Clinical data were collected from 12 spontaneously expectorating CF patients who cultured <i>M abscessus</i> in the sputum since they were first infected with <i>M abscessus</i>, and 24 matched controls who have CF, but never been infected with <i>M abscessus</i>. Student unpaired t-test was used to compare the mean forced expiratory volume (FEV<sub>1</sub>) per year between the two groups. <h3>Results</h3> Data from 36 individuals were studied. Cases and controls were well matched. Mean absolute decline in FEV<sub>1</sub> was 100 ml/year (SD±0.19) in cases and 79 ml/year (SD±0.19) in controls. Student unpaired t-test was not significant (0.73). Mean absolute percentage predicted decline in FEV<sub>1</sub> was 3.85% (SD±5.62) in cases and 2.78% (SD±6.58) in controls. Student unpaired t-test was not significant (0.62). <h3>Conclusion</h3> These results indicate that there is a small decline in mean FEV<sub>1</sub> per year between the two groups; <i>M abscessus</i> and the controls, but the difference is statistically and clinically insignificant.
516 EFAVIRENZ INDUCES ENDOPLASMATIC STRESS IN HUMAN HEPATIC CELLS BY A MECHANISM DIFFERENT THAN THAT ELICITED BY THE PHARMACOLOGICAL INDUCER THAPSIGARGIN
Authors: F. Alegre, M. Polo, L.J. Gómez-Sucerquia, H.A. Funes, A. Blas-Garcia, J.V. Esplugues, N. Apostolova
Journal: Journal of Hepatology (2013)
THU0026 Genetic Variation Near IRF8 is Associated with Serologic and Cytokine Profiles in Systemic Lupus Erythematosus and Multiple Sclerosis
Authors: B. Chrabot, S. N. Kariuki, M. Zervou, X. Feng, J. Arrington, M. Jolly, D. T. Boumpas, A. T. Reder, G. N. Goulielmos, T. B. Niewold
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Alleles of IRF8 have been associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). While type I interferon (IFN) is thought to be causal in SLE, type I IFN is used as a therapy in MS. <h3>Objectives</h3> We investigated whether the IRF8 alleles were associated with differences in serum IFN in SLE or MS. <h3>Methods</h3> Single nucleotide polymorphisms (SNPs) in IRF8 (associated with SLE and MS respectively) were genotyped in 627 SLE patients of African-American, European-American, and Cretan origin, 73 MS patients, and matched controls. Serum type I IFN was measured using a functional reporter cell assay. <h3>Results</h3> The MS-associated rs17445836 G allele was associated with the presence of anti-dsDNA autoantibodies in SLE patients across all ancestral backgrounds (meta-analysis OR=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and the subgroup of MS patients with secondary progressive MS. The rs17445836 G allele was associated with decreased type I IFN-induced gene expression in PBMC from SLE patients who lacked anti-dsDNA antibodies. No associations were observed with the rs12444486 allele. <h3>Conclusions</h3> The rs17445836 G allele was associated with decreased type I IFN responses in both SLE and MS patients. The association of this allele with low IFN SLE and with MS, a condition characterized by low circulating type I IFN levels, suggests that this allele is associated with autoimmunity in the setting of low type I IFN levels. These data also suggest a role for this allele in humoral autoimmune responses. <h3>Disclosure of Interest</h3> None Declared
Elevated Circulating Levels of Tumor Necrosis Factor in Severe Chronic Heart Failure
Authors: Beth Levine, Jill Kalman, Lloyd Mayer, Howard M. Fillit, Milton Packer
Journal: New England Journal of Medicine (1990)

Although cachexia often accompanies advanced heart failure, little is known about the causes of the cachectic state. To assess the potential role of tumor necrosis factor in the pathogenesis of cardiac cachexia, we measured serum levels of the factor in 33 patients with chronic heart failure, 33 age-matched healthy controls, and 9 patients with chronic renal failure.
Bronchiectasis: Treatment and Prevention
Authors: Theodore L. Badger
Journal: New England Journal of Medicine (1947)

BRONCHIECTASIS is protean in its expressions as it is sometimes obscure in its origin. The clinical picture varies in individual patients, but common to the severer cases is a history of harassing, recurrent pulmonary infection, head colds or sinusitis that "goes dowm into the chest," to remain for weeks with a productive cough, or one of recurrent hemoptyses or repeated attacks of pneumonia. As a rule, severe pulmonary infections date the onset of the symptoms of bronchiectasis. With great clarity patients recall childhood and adult pneumonias, measles and whooping cough, influenza and "croup" as the beginning of the pulmonary trouble. . . .
SAT0209 The Clinical and Radiographic Course of Early Undifferentiated Arthritis under Treatment is not Dependent on the Amount of Erosions at Diagnosis. Results from the Swiss Prospective Observational Cohort
Authors: R. Mueller, T. Kaegi, S.R. Haile, J. von Kempis
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To analyse whether ACR/EULAR negative early undifferentiated arthritis patients have a different course of the disease dependent on whether they can or cannot be classified as RA because of radiographic disease (as recently defined by the EULAR task force) at diagnosis. <h3>Methods</h3> For this observational study within the Swiss RA cohort SCQM, we included patients with early undifferentiated arthritis (disease duration ≤1 year), as diagnosed by the treating rheumatologist, who had not received any previous DMARDs. 2010 ACR/EULAR criteria negative patients were separated into 2 groups (radiographic vs. non radiographic arthritis) depending on whether or not they had radiographic changes recently defined as erosive disease by a EULAR task force (≥3 erosions). The effect of a positive Erosion score (was analysed for DAS-28 and HAQ scores using linear mixed models with random slope and random intercept, and adjusted for various baseline factors in a univariate fashion. Slopes of the Ratingen score after diagnosis were compared between groups using analysis of variance (ANOVA). The primary outcome measure was the radiographic progression detected employing the Ratingen erosion score. HAQ and DAS 28 were used as secondary outcome measures. The average observation period was 4 years. <h3>Results</h3> A total number 592 patients was analysed. 240 were not classifiable as RA by application of the 2010 ACR/EULAR criteria at baseline. 133 of these patients had radiographic arthritis and 50 non-radiographic arthritis. In 57 patients radiographs at the first visit were not available. Treatment was initiated in all patients with DMARDs, mostly MTX. There were no significant differences in the therapeutic strategies between radiographic and non-radiographic patients. No differences in DAS 28 and HAQ scores were found during follow up over 4 years. The average erosion scores were higher among patients with initially radiographic arthritis throughout the study. The progression of erosion scores over time, however, was higher in initially non radiographic arthritis patients (3.3 erosions/year vs. 0.4, resp., p&lt;0.0001). <h3>Conclusions</h3> The clinical and radiographic progression of early undifferentiated arthritis under treatment was not dependent on the presence of 3 or more erosions (i.e. the definition of radiographic disease by the EULAR taskforce) at diagnosis in our cohort. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2034
c-Myb Enhances Breast Cancer Invasion and Metastasis through the Wnt/β-Catenin/Axin2 Pathway
Authors: Yihao Li, Ke Jin, Gabi W. van Pelt, Hans van Dam, Xiao Yu, Wilma E. Mesker, Peter ten Dijke, Fangfang Zhou, Long Zhang
Journal: Cancer Research (2016)

Abstract The molecular underpinnings of aggressive breast cancers remain mainly obscure. Here we demonstrate that activation of the transcription factor c-Myb is required for the prometastatic character of basal breast cancers. An analysis of breast cancer patients led us to identify c-Myb as an activator of Wnt/β-catenin signaling. c-Myb interacted with the intracellular Wnt effector β-catenin and coactivated the Wnt/β-catenin target genes Cyclin D1 and Axin2. Moreover, c-Myb controlled metastasis in an Axin2-dependent manner. Expression microarray analyses revealed a positive association between Axin2 and c-Myb, a target of the proinflammatory cytokine IL1β that was found to be required for IL1β-induced breast cancer cell invasion. Overall, our results identified c-Myb as a promoter of breast cancer invasion and metastasis through its ability to activate Wnt/β-catenin/Axin2 signaling. Cancer Res; 76(11); 3364–75. ©2016 AACR.
Case 32-2015
Authors: Michael K. Mansour, Jeanne B. Ackman, John A. Branda, Richard L. Kradin
Journal: New England Journal of Medicine (2015)

A 57-year-old man was admitted to the intensive care unit in the winter because of severe pneumonia and acute hypoxemic respiratory failure. One month earlier, he had returned from a trip to Southeast Asia. Diagnostic procedures were performed.