tbuckley/cabot-search huggingface dataset:
Abstract 4136: Development of a new and sensitive detection technology for galectin cancer proteins.
Authors: Hilde van Hattum, Rob Ruijtenbeek, Riet Hilhorst, Roland Pieters
Journal: Cancer Research (2013)

Abstract The galectin protein family consists of fifteen galactoside-binding proteins that are present in all classes of life where they function as cell-cell and cell-matrix interaction mediators. Galectins are however also highly overexpressed in various processes related to cancer, including apoptosis, angiogenesis and metastasis. Galectins are therefore excellent targets for tumor diagnostics and medical prognostic purposes. Current proteomic tools, e.g. Polymerase Chain Reaction (PCR) and Enzyme-linked Immunosorbent Assay (ELISA), are based on protein abundance rather than protein activity. In contrast, we have developed a galectin detection assay that visualizes galactoside-binding, i.e. functional, galectins using PamChip® microarray technology. Firstly, antibodies directed against different galectins are efficiently immobilized on the microarray surface by the Fc-binding protein A/G. Then galectin-1 was captured from a spiked cell lysate that is added to the microarray and the unbound proteins are washed away. The galectin presence is subsequently quantified with a general fluorescent ligand that is only bound by active galectins. Several ligands based on lactose and lactosamine were designed and tested. With the best ligands it was possible to detect galectin quantities in the low nanogram range using only 1 μg or less of precious anti-galectin antibodies per measurement. These results are truly promising for the use of the newly developed galectin detection technology in a clinical setting. Citation Format: Hilde van Hattum, Rob Ruijtenbeek, Riet Hilhorst, Roland Pieters. Development of a new and sensitive detection technology for galectin cancer proteins. [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 4136. doi:10.1158/1538-7445.AM2013-4136
Estrogen Resistance Caused by a Mutation in the Estrogen-Receptor Gene in a Man
Authors: Eric P. Smith, Jeff Boyd, Graeme R. Frank, Hiroyuki Takahashi, Robert M. Cohen, Bonny Specker, Timothy C. Williams, Dennis B. Lubahn, Kenneth S. Korach
Journal: New England Journal of Medicine (1994)

Mutations in the estrogen-receptor gene have been thought to be lethal. A 28-year-old man whose estrogen resistance was caused by a disruptive mutation in the estrogen-receptor gene underwent studies of pituitary-gonadal function and bone density and received transdermal estrogen for six months. Estrogen-receptor DNA, extracted from lymphocytes, was evaluated by analysis of single-strand-conformation polymorphisms and by direct sequencing.
Stable Transduction of Actively Dividing Cells via a Novel Adenoviral/Episomal Vector
Authors: H. Leblois, C. Roche, N. Di Falco, C. Orsini, P. Yeh, M. Perricaudet
Journal: Molecular Therapy (2000)

Many gene therapy indications would benefit from vectors capable of achieving efficient in vivo delivery and long-term transgene expression in either dividing or nondividing cells. Such vector systems are not yet available. To achieve both goals, we have used noncytotoxic E1- and E4-deleted adenoviral vectors as vehicles for delivering an Epstein–Barr virus-based self-replicating episome (replicon) via Cre/loxP site-specific recombination. Co-infection of human cells with a proreplicon-encoded and a Cre-expressing adenovirus resulted in efficient delivery and excision of a functional replicon in the absence of vector-induced cytotoxicity. In addition, replication and nuclear retention of the replicon in the cell progeny translated into a prolonged transgene expression in actively dividing cells, both in vitro and in vivo. Combining desired features from different viruses within a single hybrid vector system should expand the range of clinical indications currently amenable to gene transfer. Many gene therapy indications would benefit from vectors capable of achieving efficient in vivo delivery and long-term transgene expression in either dividing or nondividing cells. Such vector systems are not yet available. To achieve both goals, we have used noncytotoxic E1- and E4-deleted adenoviral vectors as vehicles for delivering an Epstein–Barr virus-based self-replicating episome (replicon) via Cre/loxP site-specific recombination. Co-infection of human cells with a proreplicon-encoded and a Cre-expressing adenovirus resulted in efficient delivery and excision of a functional replicon in the absence of vector-induced cytotoxicity. In addition, replication and nuclear retention of the replicon in the cell progeny translated into a prolonged transgene expression in actively dividing cells, both in vitro and in vivo. Combining desired features from different viruses within a single hybrid vector system should expand the range of clinical indications currently amenable to gene transfer.
Abstract 1810: PTEN association with mTOR pathway activation and outcomes in bladder cancer
Authors: Mohammed Orloff, Paul Elson, Yi-Ran Yang, Charis Eng, Donna E. Hansel
Journal: Cancer Research (2010)

Abstract Background: We have recently identified increased mTOR pathway activation in urothelial carcinoma of the bladder (UCC). We next sought to determine the relationship of PTEN, an upstream negative mediator of the mTOR pathway, to mTOR activity and outcomes in UCC patients. Methods: Patients with UCC (n=118) were examined for PTEN expression, including intensity of expression (0 no expression, 1+ low, 2+ moderate, 3+ intense expression) and predominant subcellular localization (nuclear, non-nuclear). Results were correlated with the presence of lymph node (LN) metastases, recurrence-free survival (RFS) and overall survival by univariate and multivariate analysis. PTEN intron/exon mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE) and mutational status was correlated with PTEN protein expression in a subset of 91 specimens. Results: The majority of patients (91/118; 81%) demonstrated moderate to intense expression of PTEN, with PTEN loss in only 2 patients. PTEN was primarily localized to the nucleus in 30/116 (26%) patients, with some level of nuclear PTEN staining in 74/116 (64%) of patients. In LN metastases, reduced PTEN intensity was associated with an increased percentage of phospho-mTOR cells (p=0.02). PTEN mutational analysis identified 3 variants (c.132C&amp;gt;T, c.511C&amp;gt;G, c.892C&amp;gt;G) which were associated with absent PTEN protein expression and diffuse phospho-mTOR expression. Reduced RFS was correlated with positive surgical margins (p=0.09), carcinoma in situ (p=0.09) and nuclear PTEN (p=0.08). Reduced overall survival was significantly associated with metastases (p=0.04) and nuclear PTEN expression (p=0.04). Stepwise multivariable analysis showed an association between reduced RFS and LN metastases (p=0.03), carcinoma in situ (0.05) and nuclear PTEN (p=0.07). Conclusions: Alterations in PTEN expression and subcellular localization appear to mediate mTOR pathway activity in bladder cancer cells, although few mutations appear to account for reduced PTEN expression. Nuclear localization of PTEN is a relatively new finding and its function in mediating cancer behavior is under investigation. Our finding of worsened outcomes with nuclear PTEN localization warrant further functional investigation. 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 1810.
SAT0003 Quantitative Monocyte CD64 (MCD64) Expression is Useful Biomarker for Disease Activity in Systemic Lupus Erythematosus (SLE) Patients: Table 1.
Authors: A. Yura, S. Tsuji, A. Kitatoube, A. Kikuchi-Taura, M. Katayama, A. Watanabe, S. Teshigawara, M. Yoshimura, E. Kudo-Tanaka, Y. Harada, M. Matsushita, Y. Katada, S. Ohshima, J. Hashimoto, Y. Saeki
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Interferon (IFN)-α has been largely implicated in the ethiopathogenesis of SLE. The activation of IFN-α might be important in the prognosis and activity assessment of the disease. CD64 (FcγRI) is upregulated on monocytes as a response to IFN-I<sup>1</sup>. Flow cytometry analysis of mCD64 expression (Mean Fluorescence Intensity) is a convenient and rapid approach for estimating IFN-α levels in SLE patients. Additionally, macrophage colony-stimulating factor (M-CSF), which is involved in the differentiation of monocyte/macrophage, affects CD64 expression on monocyte<sup>2</sup> has been reported to increase in levels in SLE patients,<sup>3</sup> and is also involved in SLE disease activity<sup>4</sup>. mCD64 can be the quantified easily and the measurement is consistent among the respective facilities. However, the quantitative mCD64 of SLE patients has not been reported. <h3>Objectives</h3> We investigated the levels of mCD64 by quantitative flow cytometry to assess the usefulness of it as a SLE disease activity biomarker. <h3>Methods</h3> 30 SLE patients (10 active SLE, 20 inactive SLE) and 20 healthy controls (HC) were in this study. SLE disease activity was evaluated using by SLE-Disease Activity Index (SLEDAI) score. mCD64, SLE activity biomarkers (anti-DNA antibody and complement titer (CH50)), IFN-α and M-CSF were measured in SLE patients. mCD64 was measured by a quantitative flow cytometry using fluorescene microbeads. INF-α and M-CSF levels were measured using an enzyme-linked immunoabsorbent assay (ELISA). Correlational analysis between levels of mCD64, SLEDAI, SLE activity biomarkers, INF-α and M-CSF in each group were evaluated. <h3>Results</h3> Disease activity markers are shown Table 1. The variables with significant difference between active SLE and inactive SLE were SLEDAI (p&lt;0.05), CH50 (p&lt;0.05), anti DNA antibody (p&lt;0.05), mCD64 (p&lt;0.05), IFN-α (p&lt;0.05), M-CSF (p&lt;0.05).mCD64 levels were correlated with SLEDAI (r=0.6669, p&lt;0.001), anti-DNA antibody (r=0.6887, p&lt;0.05) and CH50 (r=-0.6928, p&lt;0.001), but were not correlated with C3 or C4 levels (data not shown). Further, mCD64 levels were correlated with IFN-α (r=0.6089, p&lt;0.001) and M-CSF (r=0.64443, p&lt;0.001) <h3>Conclusions</h3> This study suggests that quantitative CD64 molecules expressed on monocytes can be a useful disease activity biomarker in SLE patients. <h3>References</h3> Li, Y. et al. Arthritis Research &amp; Therapy 2010, 12:R90 Ji XH et al. Acta Pharmacol Sin. 2004; 25(10): 1361-5 Yang PT et al. Ann Rheum Dis. 2008, 67(3): 429-30 Tsuji S. et al. The Journal of Tokyo Medical University vol.70, No.1: 151-8 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2824
IN-HOSPITAL AND LONG-TERM OUTCOMES OF PERCUTANEOUS CORONARY INTERVENTIONS IN ANEMIC PATIENTS
Authors: Mohammed Al-Hijji, Malcolm Bell, Abdallah El Sabbagh, Jae Yoon Park, Gurpreet Sandhu, Rajiv Gulati, Joshua Slusser, Ryan Lennon, Guy Reeder, Charanjit Rihal, Mandeep Singh
Journal: Journal of the American College of Cardiology (2016)
The deficit state in first-episode schizophrenia
Authors: D I Mayerhoff, A D Loebel, J M Alvir, S R Szymanski, S H Geisler, M Borenstein, J A Lieberman
Journal: American Journal of Psychiatry (1994)

The prevalence, clinical correlates, and outcome of the deficit syndrome were determined for 70 patients ascertained in their first episode of schizophrenia and then followed through their recovery.Patients were treated in a standardized manner and underwent baseline assessments of symptoms and adverse effects that were repeated at intervals throughout their inpatient and subsequent outpatient course. Forty-seven patients were followed for a minimum of 6 months after remission of their positive symptoms, allowing for an assessment of their deficit syndrome status.Using modified criteria of Carpenter et al. for the deficit syndrome, the authors found that two patients (4%) met all criteria for the deficit syndrome, nine (19%) had deficit symptoms (questionable deficit state), and 36 (77%) had no deficit symptoms. When patients who had not fully remitted or had remitted for less than 6 months were included, seven (10%) met deficit syndrome criteria, 11 (16%) had deficit symptoms, and 52 (74%) had no deficit symptoms.The prevalence of the deficit syndrome in first-episode schizophrenia varies depending on the criteria used and is lower than that previously described in more chronic patient samples. Patients without deficit symptoms had better premorbid functioning and a better global outcome than patients with deficit symptoms.
A5.5 Comorbidities associated with psoriatic arthritis - a cross sectional study
Authors: N Haque, RJ Lories, K de Vlam
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Objectives</h3> Psoriatic arthritis (PsA) is a chronic inflammatory joint disease that develops in 6%–48% of the patients with Psoriasis and linked to other health concerns such as obesity, type II diabetes, dyslipidemia, hypertension and cardiovascular diseases. This association can be attributed to the chronic inflammatory process but also to shared genetic susceptibility among these diseases. The role of these metabolic disturbances in the pathogenesis, severity and progression of PsA remains unclear. Datasets about comorbidities in patients with PsA remain scarce. We therefore analysed comorbidities in PsA patients and compared them with other types of SpA. <h3>Methods</h3> Study participants were taken from the Spondyloarthritis Registry at the Division of Rheumatology, University Hospitals Leuven which includes 262 PsA and 256 other SpA patients, in clinical follow-up and contains all demographic, medical and laboratory information. The patients were grouped depending on their diagnosis and analysed on the basis of age, gender, education, workstatus, disease duration, treatment, type and number of comorbidities. The data were analysed using chi-square test, t-test, Fisher exact test and logistic regression model with correction for confounding factors (age, gender, disease duration, medication). <h3>Results</h3> Out of 518 patients (62.74% males, 37.25% females), 53.66% were found to have comorbidities. On one hand PsA patients were significantly older than other SpA patients (mean = 58.8 years vs. 44.9 years) while on the other hand SpA patients had significantly longer disease duration when compared to PsA patients (14.10 years vs. 7.12 years) (p &lt; 0.05). The PsA group was found to have more comborbidities as compared to SpA (p &lt; 0.05) and this difference remained significant using logistic regression model (OR: 1.71, p = 0.01). The cardiovascular and metabolic comorbidities were significantly higher in the PsA group as compared to SpA (p &lt; 0.01). Coronary artery disease, hypertention, hyperlipidemia, malignancy and metabolic syndrome showed a marked difference between the 2 groups (p &lt; 0.05). All these differences among the two groups remained significant even using logistic regression model (p &lt; 0.001). We could not find any relation of work status, medication and education with prevalence of comorbidites. <h3>Conclusion</h3> There is a significant increase in cardiovascular and metabolic comorbidities including malignancy in patients with PsA as compared to SpA, irrespective of demographic factors, disease duration and type of treatment. Conventional confounders such as age, gender, disease duration, therapy could not explain the difference. The cause for this increase is not known but might be specifically disease related and further research to understand the epidemiological and molecular causes hereof is necessary.
SP0057 Biologics in Lupus: Wihch and for Whom?
Authors: R. F. Van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Biologics in lupus: which and for whom? With the regulatory approval of belimumab it may be said that the treatment of SLE has (finally!) entered the biologic age. In addition to this approved agent several other biologics have been used off-label, most notably rituximab. Two large randomized clinical trials of belimumab achieved their primary endpoints, whereas two trials each with rituximab and abatacept were nominally negative. However, in some of these trials trends were observed that suggest efficacy may nonetheless be present in certain subsets of patients. Several other biologics are currently in phase II or III clinical trials. So clinicians face important questions in the management of their patients: which biologics to consider, and for whom. In this lecture, I will present some of the evidence that may help clinicians decide on these issues and use clinical cases to illustrate the certainties and uncertainties of biologics in SLE. <h3>Disclosure of Interest</h3> R. Van Vollenhoven Grant/research support from: AbbVie, BMS, GSK, MSD, Pfizer, Roche, UCB, Consultant for: AbbVie, BMS, GSK, Lilly, MSD, Pfizer, Roche, UCB
Abstract 1616: The anti-tumor effect of TAE226, dual inhibitor of FAK and IGF-IR, on non-small-cell lung cancer with <i>EGFR</i> mutation
Authors: Hiroki Otani, Shinichi Toyooka, Munenori Takaoka, Masakiyo Sakaguchi, Tsuyoshi Ueno, Hiromasa Yamamoto, Junichi Soh, Takafumi Kubo, Hiroaki Asano, Kazunori Tsukuda, Masaomi Yamane, Takahiro Oto, Katsuyuki Kiura, Nam-ho Huh, Yoshio Naomoto, Shinichiro Miyoshi
Journal: Cancer Research (2010)

Abstract Background: TAE226 is the small molecule inhibitor that has been originally considered to inhibit focal adhesion kinase (FAK) and insulin-like growth factor-I receptor (IGF-IR). FAK and IGF-IR have been reported to be up-regulated in non-small cell lung cancer (NSCLC), suggesting their important roles on pathogenesis of NSCLC. In this study, we examined the anti-tumor effect of TAE226 on NSCLC cells in vitro and in vivo. Methods: We used NSCLC cell lines consisting of 4 EGFR-mutant cell lines (PC9, H3255, HCC827, H1975) and 3 EGFR-wild type cell lines (H1819, H1299, A549). We also used PC9-derived gefitinib-resistant cell line (RPC9). Anti-proliferative effect of TAE226 was examined with MTS assay. The status of EGFR and its downstream molecules was analyzed by Western blotting. The binding affinity of TAE226 to EGFR protein in the presence of ATP was compared between mutant and wild type EGFR proteins. The effect of TAE226 on xenograft mouse models was examined. Results: The value of IC50 (µmol/L) for EGFR-mutant cells (PC-9, H3255, HCC827, H1975 [T790M], and RPC-9 [T790M]) ranged from 0.086 to 0.31 and that of EGFR wild type cells (H1819, H1299, and A549) ranged from 1.4 to 4.7, indicating that EGFR-mutant cells are sensitive to TAE226. Western blotting assay showed that TAE226 preferentially inhibited phospho-EGFR and phospho-AKT. The binding affinity of TAE226 to mutant EGFR protein was 1000 times higher compared with wild-type EGFR protein. TAE226 via oral administration with dose of 30 mg/kg and 60 mg/kg exhibited significant inhibition of tumor growth in EGFR-mutant tumors compared with EGFR-wild type tumors without major toxicity or weight loss. These results suggested that safety of TAE226 within the treatment dose for EGFR-mutant cells in vivo. Conclusions: We indicated that TAE226 showed anti-tumor effect on EGFR-mutant cells and overcame resistance to gefitinib. Our results suggest that TAE226 will be expected as a novel strategy for NSCLC with EGFR mutation regardless of the presence of secondary T790M mutation. 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 1616.
Abstract 431: Laminin-511 regulates melanoma cell function and tumor growth
Authors: Ling Tang, Tengjiao Cui, Jie Li
Journal: Cancer Research (2011)

Abstract Laminin family proteins are major non-collagenous components of basement membranes and have been found to be involved in modulating cell behavior. Laminin-511, composed of α5, β1, γ1 chains, is a major component of basement membrane of epithelia and blood vessels. Our lab has recently found increased expression of laminin-511 in malignant tumors. It has been found that tumor cells can synthesize and secrete laminin matrix to modify cellular environment and promote cell invasion. To explore the potential role of laminin-511 in melanoma, we blocked the expression of laminin-511 in human melanoma cell line SK-Mel-28 using RNA silencing strategy by transducing cells with lentiviral vector carrying laminin α5 chain specific shRNA (Lenti-Lα5 shRNA). Our data demonstrated that blocking the expression of laminin-511 significantly inhibited melanoma cell proliferation, attachment, migration and invasion in vitro, as well as tumor growth in vivo. In melanoma cells transduced with Lenti-Lα5 shRNA, compared with control melanoma cells, in cell proliferation analysis the total viable cells were 34.49% and 26.28% reduced on day 3 and day 5, respectively; in cell attachment assay the cell binding ability was decreased by 36.4%, 37.65% and 36.2% at 15, 30 and 60 minutes, respectively; in a chamber migration assay the cell migratory rate was dramatically down 90% at 24 hours; and in a Metrigel invasion assay the cell invasive capacity was markedly reduced by 89% at 24 hours. Furthermore, blocking laminin-511 expression significantly reduced tumor growth in vivo in nude mice. 18 tumors grew out of 20 injections with average volume 206 mm3 8 weeks post injection in cells tranduced with Lenti-Lα5 shRNA compared with 20 tumors out of 20 injections with average volume 590 mm3 in control cells. These findings revealed that laminin-511 plays important roles in melanoma cell function and tumor growth. In addition, our results strongly indicate laminin-511 a potential target for melanoma therapy. 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 431. doi:10.1158/1538-7445.AM2011-431