tbuckley/cabot-search huggingface dataset:
Abstract 4808: SIAH2-dependent proteolysis in cell migration, tumor growth, and cancer metastasis
Authors: Yang Liao, Rebecca R. Schmidt, Zandra Walton, Amy H. Tang
Journal: Cancer Research (2010)

Abstract The dismal prognosis of patients diagnosed with invasive and metastatic cancer points to our limited arsenal of effective anticancer therapies. The central importance of EGFR/HER2/RAS pathway activation has been well established in neoplastic transformation and tumorigenesis. An important goal in cancer biology is to identify novel and effective means to inhibit activated EGFR/HER2/K-RAS signals and reverse malignant transformation, tumor growth and cancer metastasis. SIAHs are the human homologs of Drosophila Seven-In-Absentia (SINA), an evolutionarily conserved RING E3 ligase that is an essential downstream signaling module and critical “gatekeeper” required for RAS signal transduction in human cancer cells. By targeting the most downstream signaling module identified in the RAS pathway - the SIAH2 proteolytic machinery, we are able to block tumorigenesis and metastasis in multiple of the most aggressive forms of human cancer cells known in athymic nude mice. Although we are fully cognizant of the systemic limitation in the xenograft models and incomplete mimicry of the full-spectrum metastatic processes observed in athymic nude mice, we are encouraged by the impressive anti-SIAH2-based tumor suppression in these preclinical studies. In this study, we aim to identify the molecular mechanism(s) of SIAH2 action in human cancer cells. To delineate SIAH2 function in cancer, through a proteomic approach, we identified three endogenous LIM domain proteins, TRIP6/FHL2/LPXN, as the bona fide SIAH2-interacting proteins isolated from the most aggressive human cancer cell lines (A549, MiaPaCa and MDA-MB-435 cells) in parallel. We provide extensive biochemical evidence to show that TRIP6/FHL2/LPXN are bona fide SIAH2 substrates. These new SIAH2 substrates can successfully rescue cell motility and viability defects observed in SIAH2-deficient cancer cells, suggesting that these focal adhesion proteins may represent one of many diverse signaling modules that function downstream of SIAH2 in mediating aspects of RAS-dependent signaling in normal development and cancer. Our results suggest In response to ERBB/RAS activation, SIAH2 E3 ligase modulates cell junction, adhesion and migration by targeting focal adhesion proteins for ubiquitin-mediated proteolysis to promote cell migration, tumorigenesis and metastasis in human cancer cells. The identification of SIAH2-mediated focal adhesion and cell junction modulation may have important implications in cancer biology to explain the well-documented modulations in focal adhesion, cell junction and motility in response to ERBB/RAS activation in human cancer cells. 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 4808.
WEIGHT LOSS IS SUPERIOR TO EXERCISE IN IMPROVING THE ATHEROGENIC LIPID PROFILE IN AN OVERWEIGHT, SEDENTARY POPULATION WITH CORONARY ARTERY DISEASE: THE RANDOMIZED CUT-IT TRIAL
Authors: Lene Roerholm Pedersen, Rasmus Olsen, Rosemary Walzem, Steen Bendix Haugaard, Eva Prescott
Journal: Journal of the American College of Cardiology (2015)
Acute Suppurative Tenosynovitis of the Hand
Authors: J. Edward Flynn
Journal: New England Journal of Medicine (1950)

SUPPURATIVE inflammation of the flexor tendons of the hand presents a controversial problem, and one that has not been solved surgically.The incidence and complications of acute suppurative tenosynovitis have decreased since the advent of antibiotics. However, this serious infection is still encountered too frequently.Analysis of StudyThe material studied consisted of 100 cases of acute pyogenic infection of the flexor tendon sheaths of the hand, previous to antibiotics, and 50 cases since the advent of antibiotics, in which patients were treated at the Boston City Hospital.The origin of the infection has not changed since the advent of . . .
AB0562 New concept of squaring score to evaluate 1st sacrum in modified stoke ankylosing spondylitis spinal score; mr correlation
Authors: S. Lee, K.-B. Joo, K.-S. Na, T.-H. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In assessment of mSASSS, the spinal squaring is an important factor of scoring. However, it is difficult to evaluate the sacral squaring in mSASSS <h3>Objectives</h3> This study aimed to suggest the new concept of squaring score with loss of concavity in the anterior border of 1<sup>st</sup> sacrum and to evaluate the reproducibility of the new squaring score of 1<sup>st</sup> sacrum in the modified Stoke AS Spinal Score (mSASSS) with correlation of MR <h3>Methods</h3> The study group comprised 26 healthy subjects and 80 patients with AS. Two experienced radiologists assessed the scoring of 1<sup>st</sup> sacrum in mSASSS using old and new concepts independently and assessed the MR score in consensus. And, the new concept of squaring score was evaluated whether to correlate with MR scoring of 1<sup>st</sup> sacrum. The frequencies of squaring, sclerosis or erosion of 1<sup>st</sup> sacrum were respectively obtained with old and new concepts, and the differences between the control and AS groups were statistically analyzed. <h3>Results</h3> The frequency of squaring for 1<sup>st</sup> sacrum in the control group was 15.4% and in the patients group was 36.3%. There were statistically significant difference in the squaring score in the 1<sup>st</sup> sacrum between two groups. Kappa interobserver reliability coefficients with old and new concepts were 0.79 and 0.64, respectively. The concept of loss of concavity showed good agreement with MRI (kappa value, 0.66). <h3>Conclusions</h3> Loss of concavity in the anterior border of 1<sup>st</sup> sacrum is useful for scoring of squaring in the 1<sup>st</sup> sacrum in mSASSS and shows good reproducibility <h3>Disclosure of Interest</h3> None Declared
Abstract LB-358: Carcinogen-induced epigenetic silencing of miR-205 and miR-200 family promotes EMT and transformation of lung epithelial cells
Authors: Carmen S. Tellez, Daniel Juri, Kieu Do, Amanda Bernauer, Cindy Thomas, Shuguang Leng, Mathewos Tessema, Leah A. Damiani, Steven A. Belinsky
Journal: Cancer Research (2010)

Abstract An in vitro carcinogen-induced transformation model was developed using immortalized bronchial epithelial cells (HBECs) to identify key molecular changes in preneoplastic lung epithelial cells that occur during the development of lung cancer in smokers. HBECs were treated for twelve weeks (one exposure per week) with low-doses of tobacco carcinogens (MNU and BPDE) that resulted in transformation from genotoxic stress (DNA damage). The HBECs displayed a morphological change consistent with an epithelial-to-mesenchymal transition (EMT) after 4 weeks of carcinogen treatment that persisted in colonies that were recovered and expanded from soft agar (transformed cell line). Expression of mesenchymal markers vimentin, fibronectin, and N-cadherin increased significantly, while the epithelial marker E-cadherin was significantly decreased. The most notable changes associated with EMT included 4 - 55 fold reduced expression of miR-200b, -200c, and -205 that correlated with 2-1500 fold increased expression of E-box binding transcription factors (SNAI1, ZEB1, ZEB2) and basic helix-loop-helix transcription factor (TWIST1). Restoring the expression of miR-200b, -200c or -205 in carcinogen transformed cells prevented growth in soft agar; meanwhile the cells maintained a fibroblast-like mesenchymal appearance. Levels of DNA methyltransferase 1 (DNMT1) protein also increased significantly during carcinogen treatment and stable knockdown of DNMT1, but not DNMT3A and DNMT3B prior to carcinogen prevented EMT and transformation. ChIP for H3K4me2 (indicative of active/open chromatin) revealed a progressive decrease of this mark at the promoters of miR-200b, -200c, and -205 over 12 weeks of carcinogen treatment and during transformation. A modest enrichment for H3K9me2 (inactive/closed chromatin mark) was observed at all time points. In contrast, H3K27me3 (indicative of inactive/closed chromatin) was enriched at the miR promoters after 4 weeks of carcinogen treatment and enrichment declined over time. Bisulfite sequencing revealed CpG DNA methylation increased from 3% to 42% in the miR-200 family and miR-205 promoters during transformation. To examine the clinical relevance of miR-200b, -200c, and -205 their expression was analyzed in lung tumors relative to distant normal lung tissue from 24 patients. Reduced expression of at least one miR was observed in 50% of lung adenocarcinomas. These findings implicate a major role for epigenetic regulation of EMT that extends beyond that of cancer metastasis to causality for development of premalignant lung cancer. Supported by ES008801. 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 LB-358.
BI-19 * PSEUDOPROGRESSION IN OLIGODENDROGLIOMAS AND MIXED OLIGOASTROCYTOMAS IS ASSOCIATED WITH POOR PROGNOSIS
Authors: A. Lin, J. Liu, J. Huang, C. Robinson, J. Simpson, M. Chicoine, R. Dacey, A. Kim, K. Rich, E. Leuthardt, G. Linette, M. Miller-Thomas, R. Schmidt, S. Dahiya, D. Tran
Journal: Neuro-Oncology (2014)

INTRODUCTION: Pseudoprogression (PsP) is a radiologic phenomenon in which treatment results in disruption of the blood brain barrier resulting in areas of contrast enhancement that is indistinguishable from true tumor progression. In glioblastoma, PsP occurs more frequently in tumors with MGMT promoter methylation and is associated with a better prognosis. We investigated whether the two recurrent genetic alterations, 1p/19q codeletions and IDH1 R132H mutation, which have prognostic significance in oligodendrogliomas (OG) and oligoastrocytomas (OA), are associated with PsP. METHODS: Institutional review board approval was granted to query a pathologic database for grade II and III OG/OA and to perform IDH1 R132H immunohistochemistry on archival material. 139 patient cases were identified, in which serial imaging was performed, records were available for review, and the tumors were treated with fractionated radiotherapy. IDH1 R132H immunohistochemistry was performed on archival material from these cases when available and their charts were reviewed for clinical data. RESULTS: PsP occurred less frequently in OG/OAs with 1p/19q codeletions (8% of tumors) than tumors without 1p/19q codeletions (27% of tumors) with an odds ratio of 0.168 and 95% CI of 0.050-0.562 when adjusting for covariables by multivariate modeling. Within the cohort without 1p/19q codeletions, the development of PsP in OG/OA was independently associated with worse survival when compared to tumors without early contrast enhancement following treatment (p = 0.0059). Additionally, within this cohort without 1p/19q codeletions, 50% of the tumors with PsP were negative for IDH1 R132H mutation by immunohistochemistry, compared to 26% negativity among tumors without early contrast enhancement. CONCLUSIONS: In this study, we are the first to show that PsP occurs more frequently in OG/OA with a worse prognosis and that PsP may have an inverse association with 1p/19q codeletions and IDH1 R132H mutation.
1428 INVERSE CHANGES IN HEPATIC EXPRESSION OF INTERFERON LAMBDA AND ALPHA AND IFNL4 GENOTYPE ARE ASSOCIATED WITH TREATMENT RESPONSE IN SOFOSBUVIR/RIBAVIRIN TREATED HCV GENOTYPE-1 SUBJECTS
Authors: E.G. Meissner, D. Bon, A. Osinusi, W. Tang, E. Herrmann, J. McHutchison, W. Symonds, H. Masur, T.R. O'Brien, L. Prokunina-Olsson, S. Kottilil
Journal: Journal of Hepatology (2013)
OP02 * THALAMIC TUMOURS IN CHILDREN: EVALUATION OF SURGICAL STRATEGY
Authors: B. Pettorini, B. Pizer, A. Kanwar, C. Chamilos, B. Zebian, C. Parks, S. Avula, C. Mallucci
Journal: Neuro-Oncology (2014)

INTRODUCTION: Indication for resection of paediatric thalamic tumours has always been debated, varying from biopsy only strategy to total resection. Thalamic tumours are considered unfavourable for resection because of high morbidity and a lack of data between extent of resection and survival. In this study we reviewed our experience with thalamic tumours since 1998 to appraise our practice and surgical strategies and to determine which factors guided treatment. METHOD: Medical records were obtained in 17 children with thalamic tumours operated on between 1998 and 2011. Age at presentation, duration and type of symptoms, radiological features, treatment received, surgical approach, follow-up and survival were recorded. Type of surgery was classified as biopsy, partial resection (<90%), subtotal resection (>90%) or total. RESULTS: The patients ranged in age from 2 to 15 (median 7.4 years). The tumours were treated by biopsy alone (stereotactically or endoscopically) in 10 cases, by biopsy followed by resection in 4 cases and resection alone in 5 cases. Partial resection was then achieved in 33% of cases, subtotal in 44% and total in 22%. The tumours were approached via transcortical transtemporal route in 7 cases and transcallosal route in 2 cases.The tumour diagnosis was pilocytic astrocytoma in 37% of cases, oligodendroglioma in 28%, astrocytoma grade II in 43%, astrocytoma grade III in 18%, glioblastoma in 6% and glioneuronal tumour in 6%. Five children suffered transient morbidity after surgery, two of them after biopsy. Two children died during follow-up. CONCLUSION: Recent improvement in imaging techniques and surgical tools make more aggressive surgery technically feasible and safe.
S118 IL-13 Induced Mouse Airway Inflammation Induces an Increase of Soluble ADAM33 in Bronchoalveolar Lavage Fluid, Which is Enzymatically Active and Associated with Bronchial Hyperresponsiveness
Authors: ER Davies, G Chen, ST Holgate, DE Davies, JA Whitsett, HM Haitchi
Journal: Thorax (2012)

<h3>Rationale</h3> The asthma susceptibility gene <i>ADAM33/Adam33</i> is associated with bronchial hyperresponsiveness(BHR) in humans and mice. Soluble ADAM33 is increased in bronchoalveolar lavagefluid (BALF) of allergic asthma patients (Lee JY et al, AJRCCM 2006 Apr1; 173(7):729–35). Its levels correlate with declining FEV<sub>1</sub>%, suggesting a role in airway remodelling in asthma. Maternal allergy orexogenous IL-13 suppresses <i>Adam33/ADAM33</i>mRNA expression but enhances ADAM33 protein processing in human embryonic and juvenile mouse lungs (Haitchi HM et al, JACI. 2009 Sep; 124(3):590–7, 597). We hypothesise thatconditional expression of IL-13 in mouse lungs induces the enzymatically active, soluble form of ADAM33 in BALF, which is associated with BHR. <h3>Methods</h3> <i></i> IL-13 expression wasinduced using Doxycycline in CCSP-rtTA/Otet-Il-13 double-transgenic (dTg) mice. Methacholine challenge and lung function measurements were performed and lungswere harvested for mRNA extraction and immunohistochemistry (IHC). BALF was obtained forWestern-blotting for ADAM33 and testing of ADAM33 enzymatic activity using a fluorescenceresonance energy transfer (FRET) peptide assay. <h3>Results</h3> There was asignificant increase in BHR to Methacholine in IL-13 expressing double transgenicmice. IHC showed an increase inbronchial smooth muscle in lungs of double transgenic mice. Similar to the RTqPCR findings in humanembryonic and juvenile mouse lungs, IL-13 suppressed <i>Adam33</i> mRNA but no difference in <i>a-smooth muscle actin</i> (<i>aSma)</i> was evident. Immunoblotting for ADAMA33 in BALF demonstrateda 76kDa band, consistent with the ADAM33 ectodomain and processed forms at38/44kDa in dTg animals. ADAM33 enzymatic activity was also significantly increased. <h3>Conclusion</h3> <i></i> The data suggest thatallergic inflammation induced by IL-13 suppresses <i>Adam33</i> mRNA expression but induces the release of soluble forms ofADAM33, yielding enzymatically active forms. The release of soluble forms may play a role in airway remodelling, potentiallyleading to BHR. We next propose to test the effect of specific ADAM33inhibitors on airway remodelling in this allergic mouse model to assess theirpotential as novel treatments for asthma.
Usefulness of the new electronic radial endoscopic ultrasonography (GF-UE260) for evaluating upper GI and Bilio-Pancreatic diseases
Authors: M Watanabe, M Kida, T Iwai, M Takezawa, H Kikuchi, M Araki, H Imaizumi, Y Yamada, K Saigenji
Journal: Endoscopy (2006)

The endoscopic ultrasonography (EUS) has been introduced in succession. It has been reported the usefulness of EUS for evaluating gastrointestinal and bilio-pancreatic diseases. The newly developed electronic endoscopic ultrasonography (GF-UE260) was introduced into clinical fields by OLYMPUS CO. It has doppler and tissue harmonic echo functions, so we can get radial images with color and power doppler function. We have investigated the usefulness of GF-UE260 for diagnosing upper GI and bilio-pancratic diseases in this paper. The GF-UE260 has switchable 5, 6, 7.5 and 10MHz frequencies. Its maximum diameter is 13.8mm. Scanning method is electronic radial, and scanning field is 360°. The ultrasonographic unit is Aloka ProSound SSD-α5 (Aloka Co., Tokyo). We had performed the GF-UE260 in 46 patient for evaluating bilio-pancreatic diseases and 20 upper GI diseases from Mar.2004 to Jur.2005. We have evaluated its image quality and usefulness in basic model and clinical examination. 1, Maneuverability of the electronic radial EUS is similar to that of the GF-UM2000. 2, Image quality of the electronic radial EUS is basically same as that of the GF-UM2000. 3. The electronic radial EUS has variable focal depths that can be adjusted by the processor.4. Color and power doppler function is helpful for evaluating pancreas tumor etc.5. Artifacts surrounding the scope is significantly improved.6. Tissue harmonic echo reduced its artifact. We concluded that the newly developed electronic radial EUS (GF-UE260) is useful for diagnosing upper GI and bilio-pancratic diseases.
AB0551 Cystatin C Associates with Disease Activity in Patients with Systemic Lupus Erythematosus Independent of Renal Function
Authors: S. Nishiyama, K. Ohashi, T. Aita, Y. Yoshinaga, S. Miyawaki
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Cystatin C (CysC) is produced at a constant rate by all nucleated cells. It is freely filtered by the renal glomeruli and reabsorbed and catabolized in the proximal renal tubules. Compared with serum creatinine level, serum CysC concentration is not affected by gender and muscle mass, and therefore provides a more accurate measure of glomerular filtration rate (GFR). Patients with systemic lupus erythematosus (SLE) often develop glomerulonephritis and their quality of life and prognosis are impaired. Anti-DNA antibody and serum compliments are used as serum markers of developing renal damage. CysC can be used for early detection of renal damage. Moreover, CysC may be associated with inflammation in SLE<sup>1</sup>. <h3>Objectives</h3> To examine whether CysC correlates with SLE disease activity. <h3>Methods</h3> Fifty-two patients with SLE (50 women and 2 men) who visited our hospital from Jun. 2012 to Apr. 2013 were enrolled. Mean age (SD) was 47.9 (13.2) years. Median (range) of SLEDAI was 2 (0-35). Average dose of steroid (prednisone equivalent) was 7.4 mg/day. Blood samples were collected and serum creatinine, adjusted calcium concentration, levels of C3 and C4, anti-DNA antibody titers, TSH, free T4, matrix metalloproteinase-3 (MMP-3), and 25-OH vitamin D were examined. Stepwise regression was used for multivariate analysis to test which factors correlated with CysC. GFR was estimated by MDRD method. <h3>Results</h3> CysC correlated with creatinine, MMP-3, free T4, and SLEDAI scores. Of 52 patients, 10 had abnormal GFR (&lt;60 ml/min) and all of them showed elevated CysC levels (&gt;0.9 mg/L). Forty-two patients with normal GFR were divided into high level of CysC (n=23) and normal level of CysC (n=19). Patients with normal GFR and high CysC showed significantly higher titers of ant-DNA antibody and higher score of SLEDAI than those with normal GFR and normal CysC. <h3>Conclusions</h3> Thyroid function affects GFR<sup>2</sup> and serum MMP-3 lever is closely associated with clinical features relevant to lupus nephritis<sup>3</sup>. Besides creatinine and these renal associated factors, CysC independently correlated with SLEDAI. Moreover, Patients with normal GFR had high titers of anti-DNA antibody and high scores of SLEDAI if their CysC levels elevated, which suggests CysC associates with SLE disease activity independent of renal function. <h3>References</h3> Lertnawapan R, et al. Lupus 2012;21:279-287. A°svold BO, et al. Eur J Endocrinol 2011;164:101-105. Kotajima L, et al. Clin Exp Rheumatol. 1998;16:409-15. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5003
Metastatic potential of Her2/neu positive and Her2/neu negative circulating epithelial tumor cells (CETC) released during primary systemic chemotherapy.
Authors: K Pachmann, O Camara, M Gajda, C Rabenstein, U Pachmann, IB Runnebaum
Journal: Cancer Research (2009)

Abstract Abstract #5031 Background: Most tumor patients do not die from the primary tumor but from metastases in vital organs. To form metastases, cells must exit from the original tumor and reach these organs mainly via blood before they can settle and grow. Peripheral blood can be regarded as a transport system for CETC. Here we report on the influence of trastuzumab on the number of CETC and the impact on metastasis formation.&amp;#x2028; Material and Methods: Tumor cells were quantified with an automated microscope (Laser Scanning Cytometer®, Icis or ScanR) from anticoagulated blood drawn before each new therapy cycle from patients treated with primary systemic chemotherapy and before and after surgery and subsequent maintenance therapy. After red blood cell lysis leucocytes were stained with PE-anti-CD45 and tumor cells with FITC-anti-EpCAM and changes registered as % increase or decrease. The response of CETC to therapy was correlated to outcome.&amp;#x2028; Results: All breast cancer patients scheduled for primary systemic treatment had CETC before therapy. The number correlated with tumor size. The variable initial decrease in cell numbers highly correlated with the final tumor size reduction in her2/neu negative patients predicting for relapse free survival. All patients responded to the subsequent taxane therapy with an increase in CETC. In her2/neu positive patients who received combined taxane/trastuzumab there was only a modest increase in CETCs whereas patients with her2/neu positive disease who received taxane only showed a steep increase in CETC. 4 her2/neu positive patients who did never receive trastuzumab all had increasing CETC numbers during the postoperative observation time and all have suffered relapse. 6/6 patients who received trastuzumab only after surgery all had decreasing CETC numbers and all are in sustained complete remission after up to 4 years. 6/15 patients showed no change or an increase in CETC in spite of trastuzumab treatment and of these 4 have suffered relapse. Most relapses occurred 1-2 years after stopping trastuzumab.&amp;#x2028; Discussion: Monitoring CETC will not only provide the earliest and most reliable indicator of successful neoadjuvant treatment and spare patients unnecessary treatment. In patients with the highly aggressive her2/neu positive tumors such cells may have an increased potential to settle and re-grow. This warrants further therapy studies to control what patients may benefit from additional or modified therapy already before metastases appear. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5031.