tbuckley/cabot-search huggingface dataset:
Abstract SY07-02: Polarity proteins in morphogenesis and metastasis
Authors: Luke Martin McCaffrey, JoAnne Montalbano, Ian G. Macara
Journal: Cancer Research (2011)

Abstract Loss of epithelial organization is a hallmark of carcinomas, but whether polarity regulates tumor growth and metastasis is poorly understood. A conserved set of polarity proteins, called PAR proteins, drives cell polarization in many contexts, and in Drosophila these proteins can function as tumor suppressors. However, to date, only Par4 (LKB1) has been implicated in human cancers. To determine whether other polarity proteins might have tumor suppressor functions in mammals, we have used lentiviruses to deliver oncogenes and shRNAs to primary murine mammary cells, which are then implanted into the cleared fat pads of isogenic host mice. Using this system, we silenced expression of the PAR3 polarity protein in the context of oncogenic Notch (NICD) or Ras. Depletion of Par3 dramatically reduced tumor latency in both models, producing tumors that were highly invasive and metastatic. Notably, the NICD/shPAR3 tumors retained epithelial character, with no evidence of epithelial-mesenchymal transition in either the primary tumors or the lung metastases. We have identified an unexpected signaling pathway that drives invasion in these tumors. Importantly, PAR3 protein expression is significantly reduced in ∼50% of human breast cancers, as compared to matched normal tissue. Together, these data provide a link between cell polarity, tissue organization, and metastasis. 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 SY07-02. doi:10.1158/1538-7445.AM2011-SY07-02
Abstract 1234: GRK2 negatively regulates IGF-1R signaling pathway and cyclins in HepG2 cells
Authors: Zhengyu Wei, Reginald Hurtt, Adam S. Bodzin, Tina Gu, Cataldo Doria
Journal: Cancer Research (2012)

Abstract G protein-coupled receptor kinase 2 (GRK2) plays a central role in the regulation of a variety of signaling pathways associated with many important cellular processes. Alternation of GRK2 expression has profound effects on cell physiological functions and induces diseases such as heart failure, rheumatoid arthritis, and cancer. In this study, we investigated the role of GRK2 in human hepatocellular carcinoma (HCC) HepG2 cells. We created a GRK2 knockdown cell line using a lentivirus containing GRK2 specific shRNA. Under IGF-1 (50 ng/ml) stimulation, HepG2 cells with reduced GRK2 expression showed increased tyrosine phosphorylation of IRS1 at the residue 612 and increased phosphorylation of Akt. We then treated the cells with gefitinib, an EGFR inhibitor. We found HepG2 cells displayed gefitinib sensitiveness with the increase of drug concentration. Moreover, gefitinib treated cells with reduced expression of GRK2 showed decreased phosphorylation of Akt in a dose dependent manner, but had relatively more IGF-1R expression. However, HepG2 cells with reduced expression of GRK2 did not display any growth difference in culture as compared with the scramble control cells. We further detected that reduced expression of GRK2 induced a small G2/M phase arrest by overexpressing cyclin A, B1, and E. DNA microarray analysis showed decreased transcription levels of IGF binding protein 1 and 4, which were confirmed by quantitative PCR analysis. Our results demonstrated that GRK2 has a role in the regulation of IGF-1R signaling pathway and involves in cell cycle progression in HCC HepG2 cells. 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 1234. doi:1538-7445.AM2012-1234
SAT0278 How useful is imaging of the SI-joints (MRI and/or X-ray) in patients with possible spondyloarthritis in the diagnostic work-up?:
Authors: R. van den Berg, M. de Hooge, V. Navarro-Compán, F. van Gaalen, M. Reijnierse, T. Huizinga, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In daily practice, the diagnostic work-up of patients with possible axial spondyloarthritis (SpA) starts with clinical and laboratory data. In many patients MRI and/or X-rays of the SI-joints (MRI-SIJ and X-SIJ) are performed to be able to diagnose patients with confidence. <h3>Objectives</h3> To investigate what the contribution is of imaging (MRI-SIJ and X-SIJ) in making a final diagnosis with confidence. <h3>Methods</h3> All patients with chronic back pain (≥3 months, ≤2 years, onset &lt;45 years) in the SPondyloArthritis Caught Early (SPACE)-cohort in our clinic underwent a diagnostic work-up according to a fixed protocol. First, medical history, physical examination and laboratory assessments, including HLA-B27 typing, were performed. Based on this information, an experienced rheumatologist diagnosed all patients as either SpA or no-SpA with a level of confidence (scale 0 (not confident at all) to 10 (very confident)). Second, imaging (MRI-SIJ and X-SIJ) was performed and a diagnosis was recorded by the same rheumatologist with a new level of confidence. For the analyses, cut-off values of ≤5 (not confident) and ≥6 (confident) were used. <h3>Results</h3> In 52/157 of the patients (33.1%), the rheumatologist was confident about the diagnosis, either SpA (n=31) or no-SpA (n=21), based on clinical and laboratory data only. Imaging was positive in 32/157 patients (20.4%). In 3/52 patients (5.7%) the rheumatologist was confident about the diagnosis no-SpA, but revised the diagnosis into confident SpA after imaging. In 9/52 patients (17.3%), the rheumatologist was confident about the diagnosis based on clinical data only, but was not confident anymore after receiving negative imaging. In 105/157 of the patients (66.9%), the rheumatologist was not confident about the diagnosis. After performing imaging, the rheumatologist was confident about the diagnosis in 73/105 patients: SpA in 21 (20.0%) patients and no-SpA in 52 (49.5%) patients. In the remaining 32 (30.5%) patients imaging did not change confidence, nor diagnosis (table). <h3>Conclusions</h3> Imaging (MRI-SIJ and/or X-SIJ) is useful for the rheumatologist in the large majority of patients with possible axial SpA, except for the patients in which the rheumatologist is confident about the diagnosis of SpA before imaging. <h3>Disclosure of Interest</h3> None Declared
Long-Term Treatment of Central Precocious Puberty with a Long-Acting Analogue of Luteinizing Hormone-Releasing Hormone
Authors: M.Joan Mansfield, Donna E. Beardsworth, Jacquelyn S. Loughlin, John D. Crawford, Hans H. Bode, Jean Rivier, Wylie Vale, David C. Kushner, John F. Crigler, William F. Crowley
Journal: New England Journal of Medicine (1983)

Original Article from The New England Journal of Medicine — Long-Term Treatment of Central Precocious Puberty with a Long-Acting Analogue of Luteinizing Hormone-Releasing Hormone — Effects on Somatic Growth and Skeletal Maturation
AB0204 Fragment of Type III Collagen Degradation May BE A Novel Serological Marker for Interstitial Lung Disease in Dermatomyositis and Polymyositis
Authors: Q. Zhao, T. Zhang, Y. Zhang, G. Wang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Interstitial collagen types III is highly resistant to proteolytic attack, due to their triple helical structure. However, it can be cleaved by matrix metalloproteinase (MMP)-9 at a specific site, resulting in the generation of specific cleavage fragments [1]. Disturbed balance of collagen metabolism is a hallmark of interstitial lung disease (ILD) [2]. <h3>Objectives</h3> Our study investigated whether matrix metalloproteinases-9-cleaved fragment of type III collagen (C3M) [3] and the amino-terminal propeptide of procollagen type III (PIIINP) [4] may be used as novel markers for ILD in polymyositis (PM) and dermatomyositis (DM). <h3>Methods</h3> Serum concentrations of C3M and PIIINP were determined by enzyme-1inked immunosorbent assay in 46 adult PM/DM patients (31 with ILD, 15 without ILD) and 19 healthy controls. The correlations between serum C3M and PIIINP levels and clinical features or laboratory examinations of PM/DM patients were investigated. <h3>Results</h3> The serum levels of C3M were 7.16±3.77ng/ml in PM/DM with ILD group, 4.56±0.84ng/ml in PM/DM without ILD group, and 4.63±0.85ng/ml, in healthy controls, respectively. Serum C3M level in ILD group was significantly higher than without ILD group and healthy controls (both <i>P</i> &lt;0.01). Positive C3M was significantly associated with ILD in PM/DM (<i>P</i>&lt;0.01). The sensitivity and specificity of positive C3M for ILD in PM/DM were 71.0% and 82.4%, respectively. The serum levels of PIIINP were 12.39±12.17ng/ml in PM/DM with ILD group, 9.57±5.67ng/ml in PM/DM without ILD group, and 8.28±4.95ng/ml, in healthy controls, respectively. Serum PIIINP level in ILD group was higher than in without ILD group and healthy controls but with no statistical significance (both <i>P</i> &gt;0.05). <h3>Conclusions</h3> C3M may be potential and useful serum marker for the diagnosis of ILD in PM/DM patients. Further investigation is needed to assess the role of PIIINP in these diseases. <h3>References</h3> Bigg HF, Rowan AD, Barker MD, Cawston TE: Activity of matrix metalloproteinase-9 against native collagen types I and III. FEBS J 2007, 274:1246-1255. Dancer RC, Wood AM, Thickett DR: Metalloproteinases in idiopathic pulmonary fibrosis. Eur Respir J 2011, 38:1461-1467. Segovia-Silvestre T, Reichenbach V, Fernandez-Varo G, Vassiliadis E, Barascuk N, Morales-Ruiz M, Karsdal MA, Jimenez W: Circulating CO3-610, a degradation product of collagen III, closely reflects liver collagen and portal pressure in rats with fibrosis. Fibrogenesis Tissue Repair 2011, 4:19. Jensen LT: The aminoterminal propeptide of type III procollagen. Studies on physiology and pathophysiology. Dan Med Bull 1997, 44:70-78. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1929
Ileo-colonic infiltration in acute myeloid leukemia
Authors: S. Rodrigues, A. Ribeiro, R. Gonçalves, M. Sobrinho-Simões, L. Leite, R. Duarte, E. Fonseca, G. Macedo
Journal: Endoscopy (2013)

A 66-year-old woman with diffuse, persistent colicky abdominal pain for the past 2 months with postprandial abdominal distension, weight loss (3 kg), asthenia, anorexia, and sporadic vomiting attended the emergency room. Blood investigations revealed hemoglobin 11.6 g/dL, platelets 82 × 109/L, C-reactive protein 135 mg/dL, and potassium 3.2 mEq/L. Computed tomography (CT) revealed thickening of the ileal wall in various intestinal loops with proliferation of mesenteric fat and increased vascularization (involving 2 cm of the terminal ileum and 40 cm of the proximal ileum), suggestive of Crohn disease. The patient's abdominal pain subsided after 3 days of antibiotics (intravenous ceftriaxone 2 g once a day and metronidazole 500 mg three times a day) and an ileocolonoscopy revealed aphthous erosion in the ascending colon and edema, erythema, and three ulcers in the terminal ileum with irregular, elevated borders ([Fig. 1]). Histological examination of the ileal and colonic biopsy specimens showed profuse blast-cell mucosal infiltration ([Fig. 2 a]). Leder staining and myeloperoxidase immunostaining ([Fig. 2 b]) confirmed the myeloid nature of the neoplastic cells. A bone marrow biopsy confirmed the diagnosis of acute myeloid leukemia (AML). The French-American-British (FAB) subtype of leukemia in this case was M1. The patient was started on chemotherapy according to the AML-17 protocol with a positive hematological response. She became asymptomatic and a repeat colonoscopy with biopsies showed no signs of disease involvement on histological examination.
OP0160 Response and drug survival of 1st TNF inhibitor in 370 patients with psoriatic arthritis in a real life setting – what is the role of co-medication with methotrexate?:
Authors: K.M. Fagerli, E. Lie, D. van der Heijde, M.S. Heiberg, S. Kalstad, E. Rødevand, K. Mikkelsen, Å.S. Lexberg, T.K. Kvien
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> It is well established that methotrexate (MTX) co-medication improves efficacy of TNF-inhibitors (TNF-i) in rheumatoid arthritis, while in ankylosing spondylitis it is widely accepted that it does not. The role of MTX co-medication in psoriatic arthritis (PsA) is still unclear. <h3>Objectives</h3> Investigate if patients receiving concomitant MTX have better responses and drug survival to their 1st TNFi. <h3>Methods</h3> Data are from the NOR-DMARD register, an observational study of adult patients with inflammatory arthropathies starting DMARD-treatment, initiated in 2000. Patients with PsA receiving their 1st TNFi, either combined with MTX or with no concomitant DMARD, were selected. Due to heterogeneous symptomatology of patients, selected outcome measures were patient and physician global assessments, MHAQ and SF-6D. Baseline characteristics and state and change at 3 months were compared by two-sample t-test and χ<sup>2</sup> test, as appropriate. 3-year drug survival was compared using Kaplan-Meier analysis with log-rank test. <h3>Results</h3> 370 patients were included in these analyses. We found significant baseline group differences regarding the percentage of patients with ≥1 swollen joint and SF6D scores (table 1). Eleven patients in the MTX combo group and 14 patients in the mono group stopped mediation before 3 months follow-up, and an additional 60 patients had not yet attended or missed their 3-month visit. Three-month states and responses were similar between the groups, with statistically significant differences only for physician global. We did however find improved 3-year drug survival in the combination group (p=0.04). <h3>Conclusions</h3> Our data did not show significant impact of MTX co-medication on responses in PsA patients completing 3 months of treatment with their first TNFi. However, drug-survival was better in patients receiving concomitant MTX. <h3>Disclosure of Interest</h3> K. Fagerli Speakers Bureau: Abbott, Roche, MSD, Pfizer, E. Lie: None Declared, D. van der Heijde: None Declared, M. Heiberg: None Declared, S. Kalstad: None Declared, E. Rødevand: None Declared, K. Mikkelsen: None Declared, Å. Lexberg: None Declared, T. Kvien: None Declared
Abstract A7: Participation of atopic condition in melanoma B16-BL6 development
Authors: G. Yanek Jimenez-Andrade, Monica Lamas, Claudia Gonzalez-Espinosa
Journal: Cancer Research (2011)

Abstract Atopy is a condition characterized by the increase of total serum immunoglobulin E (IgE) levels and a tendency to develop allergic reactions. Allergy in general and specifically atopic dermatitis seems to be associated with an increased risk of melanoma development, but those findings are not conclusive. Mast cells play a central role in allergic reactions because they can be activated by IgE-antigen-dependent crosslinking of the Fc Rl receptor. Since mast cells have been found in the periphery of solid tumors and their presence correlates with tumor angiogenesis and growth, it has been proposed that activation of mast cells may facilitate blood vessel formation and tumor development. We evaluated the melanoma growth in atopic states and the role of mast cells in this process. Since hyper-responsiveness is a critical condition in atopic states, we developed a murine model of atopic condition that allowed us to quantify the increase in the inflammatory state in mice. C57BL/6J mice were sensitized with intravenous (i.v) injection of different concentrations of a monoclonal anti-DNP IgE (SPE-7 clone). Twenty-four hours after IgE administration, atopic condition was evaluated by cutaneous passive anaphylaxis (PCA) assays. A specific antigen for the SPE-7 IgE (DNP-HSA) was i.v. injected together with in Evans blue colorant and extravasation of the colorant was quantified by standard methods. C57BL/6J control and atopic mice were inoculated subcutaneously with 0.5×106B16-BL6 melanoma cells in serum-free Tyrode's buffer 24 hours after vehicle or IgE (750 ng i.v.) administration. Tumor weight was assessed during 4 weeks after inoculation of tumor cells in the ear. Results shown that tumor growth was faster in atopic than non-atopic mice. To investigate the role of mast cells in melanoma growth in atopic condition, we evaluated the tumor weight gain in mast cell deficient Kit (Wsh/Wsh) (W-sh) and mast cell reconstituted (W-sh-rec) mice in normal and atopic conditions. Melanoma tumor growth was impaired in non-atopic and atopic W-sh mice and restored in non-atopic W-sh rec. Interestingly, melanoma growth was greater in W-sh rec atopic mice than in all the groups tested. Our results suggest that atopic condition facilitates melanoma tumor growth and that mast cells participate in this effect. This work was supported by CONACyT Grants 83079 and 79162. Scholarship 210067. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr A7.
THE ACC/AHA ASCVD RISK ESTIMATOR IS A POWERFUL PREDICTIVE TOOL IN THE EVALUATION OF PATIENTS PRESENTING TO THE EMERGENCY DEPARTMENT WITH CHEST PAIN
Authors: Kareem Niazi, Chuan Jiang, Chinedu Madu, Jessica Kvasic, Michael Khalil, Amgad Makaryus, John Makaryus
Journal: Journal of the American College of Cardiology (2016)
PRELIMINARY CLINICAL EVALUATION OF A Re-186 LABELED ANTI-CEA F(abʼ)2 ANTIBODY FRAGMENT AS A POTENTIAL RADIOIMMUNOTHERAPY AGENT.
Authors: L. Hanelin, R. Schroff, M. Fer, P. Weiden, H. Breitz, D. Fisher, P. Abrams, D. Axworthy, B. Ratliff, J-L Vanderheyden, J. Appelbaum, A. Fritzberg
Journal: Clinical Nuclear Medicine (1988)

Hanelin, L.; Schroff, R.; Fer, M.; Weiden, P.; Breitz, H.; Fisher, D.; Abrams, P.; Axworthy, D.; Ratliff, B.; Vanderheyden, J-L; Appelbaum, J.; Fritzberg, A. Author Information
PET/CT Findings in Acute Gastric Anisakiasis
Authors: Koichiro Abe, Tomonori Yoshikai, Shingo Baba, Takuro Isoda, Hiroshi Honda
Journal: Clinical Nuclear Medicine (2013)

Acute gastric anisakiasis is caused by the consumption of raw or undercooked fish containing Anisakis larvae. Although several reports have demonstrated the CT features of acute gastric anisakiasis, little is known about the FDG PET/CT findings. We report a 59-year-old woman who underwent FDG PET/CT and was finally diagnosed as having acute gastric anisakiasis. The PET/CT demonstrated focal FDG accumulation in the fornix of the gastric wall and lymph nodes in the lesser curvature and paraaortic regions.
Abstract B1: p53 isoforms, Δ133p53 and p53β, regulate aging-associated T lymphocyte senescence.
Authors: Abdul Matin Mondal, Izumi Horikawa, Sharon R. Pine, Kaori Fujita, Borivoj Vojtesek, Jean-Christophe Bourdon, Elsa Vera, David P. Lane, Maria A. Blasco, Curtis C. Harris
Journal: Cancer Research (2011)

Abstract Normal human cells undergo finite divisions and reach a state of cellular senescence, which is a critical barrier for tumor progression in vivo and contributes to organismal aging. CD8+ T lymphocytes are an excellent model to study cellular senescence in vivo. The decreased proliferative potential and cellular senescence of CD8+ T lymphocytes are associated with loss of CD28 and gain of CD57 cell surface antigens, but the mechanisms regulating these phenotypic changes are unknown. The natural isoforms of human p53 protein, Δ133p53 and p53β, play important roles in regulating replicative cellular senescence in vitro (e.g., in normal human fibroblasts) and in vivo (e.g., in colon adenomas) and in different cell types (mesenchymal and epithelial origins). In this study we show that Δ133p53 and p53β are associated with and regulate replicative cellular senescence in CD8+ T lymphocytes (hematopoietic origin), which represent a physiological setting of in vivo cellular senescence. Loss of CD28 and gain of CD57 in CD8+ T lymphocytes were associated with increased donor age in normal individuals. When stimulated to proliferate in vitro, the FACS sorted CD28+/CD57− subsets of CD8+ T lymphocytes showed highest proliferation rate, whereas CD28−/CD57+ subsets showed lowest. The loss of proliferative potential of the CD28−/CD57+ cells was also associated with the shorter telomere length than the CD28+/CD57− subsets. Importantly, Δ133p53 and p53β expression levels were significantly changed during cellular senescence of CD8+ T lymphocytes, as observed in human fibroblasts and colon adenomas. Δ133p53 levels were decreased and p53β levels were increased in the senescent CD28−/CD57+ subset compared with the proliferative CD28+/CD57− subset. During in vitro culture, FACS sorted CD8+ T lymphocytes became senescent and lost Δ133p53 expression, which was associated with the loss of CD28 expression. Moreover, in overexpression experiments, p53β cooperated with full-length p53 to inhibit cellular proliferation, and Δ133p53 enhanced the proliferative potential of the CD8+ T lymphocytes, suggesting that the p53 isoforms regulate cellular proliferation and senescence in CD8+ T lymphocytes. Our study provides insight toward understanding the mechanisms regulating physiological aging of normal human circulating T lymphocytes and thus proposes a novel approach for reinstating replicative potential and immune function of the senescent CD8+ T lymphocytes. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr B1.
Reciprocal T(7;11)(P15;P15): A Rare but Recurrent Translocation in Acute Myeloid Leukemia. Report of 3 Cases
Authors: M. Manabe, J. Okita, N. Harada, T. Takakuwa, Y. Aoyama, T. Kumura, T. Ohta, Y. Furukawa, A. Mugitani
Journal: Annals of Oncology (2013)