tbuckley/cabot-search huggingface dataset:
Pharmacodynamics of 5-Iodo-2'-deoxyuridine in VX2 Tumor-Bearing Rabbits
Authors: P. L. STETSON, Z. YANG, W. D. ENSMINGER
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article Pharmacodynamics of 5-Iodo-2'-deoxyuridine in VX2 Tumor-Bearing Rabbits Get access PHILIP L. STETSON, PHILIP L. STETSON * 1Upjohn Center for Clinical, Pharmacology and Department of Pharmacology, University of Michigan, School of MedicineAnn Arbor, MI *Correspondence to: Philip L. Stetson, Ph.D., Upjohn Center for Clinical Pharmacology, University of Michigan School of Medicine, 3700 Upjohn Center, Ann Arbor, MI 48109. Search for other works by this author on: Oxford Academic PubMed Google Scholar ZHAOMIN YANG, ZHAOMIN YANG 2Upjohn Center for Clinical PharmacologyAnn Arbor, MI Search for other works by this author on: Oxford Academic PubMed Google Scholar WILLIAM D. ENSMINGER WILLIAM D. ENSMINGER 2Upjohn Center for Clinical PharmacologyAnn Arbor, MI Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 24, 20 December 1989, Pages 1925–1926, https://doi.org/10.1093/jnci/81.24.1925 Published: 20 December 1989
Abstract 2246: Identification of genomic alterations associated with metastasis and poor prognosis in clear cell renal cell carcinoma
Authors: Jimsgene Sanjmyatav, Carsten Schwaenen, Sven Wessendorf, Marcus Kreuz, Thomas Steiner, Heiko Wunderlich, Susanne Fuessel, Kerstin Junker
Journal: Cancer Research (2010)

Abstract Introduction: Clear cell renal cell carcinoma (ccRCC) is the most frequently encountered renal malignancy with a high metastatic potential and the prognosis of patients in this subgroup is very poor. Prognostic parameters which can be used for an individual prognostic evaluation are still not available, So the aim of our study was high resolution screening of genomic imbalances of metastasized and non-metastasized primary ccRCC by array CGH in order to identify regions of DNA copy number changes significantly associated with metastasis and clinical outcome of patients. Methods: We conducted genome-wide copy number profiles in 56 primary ccRCC including 32 metastasized and 24 non-metastasized tumours by array CGH with a median resolution of 2Mbp. The median follow up of the patients was 47 months. Results: Array CGH identified 6 recurrent chromosomal aberrations: gains of 1q21.3, 12q13.11, 12q13.2 and 20q11.21q13.2 and losses of 8p11.23p12 and 9p21.3p24.1, which were significantly associated with metastasis occurrence. In multivariate analysis including these aberrations gains of 1q21.3 and of 20q11.21q13.2 and loss of 9p21.3p24.1 attained as independent predictors for metastasis in our cohort with 81.5% sensitivity and 95.8% specificity of 81.5% and 95.8%, respectively. Kaplan-Meier survival analysis showed that gains on chromosomes 7, 12, 16 and 20q and losses on chromosome 9 have a significant correlation with disease specific survival. Multivariate Cox-regression analysis revealed gains of 7q36.3 and of 20q11.21q13.2 and a loss of 9p21.3p24.1 as independent prognostic factors for patients' outcome of patients. Conclusions: Our data suggest that specific common copy number alterations in ccRCC could serve as independent predictors for metastasis occurrence and cancer specific survival in patients with ccRCC. 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 2246.
AB0498 Low Dose Pulse IV Methylprednisolone as Induction Therapy for Lupus Nephritis: A Preliminary Study:
Authors: S. Fasano, L. Gabriele Falcone, G. La Montagna, G. Valentini
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Glucocorticoids (GC) pulses (750mg/day for 3 consecutive days) represent the induction arm of lupus nephritis trial (1) and are commonly used in clinical practice. This regimen can be complicated by adverse events as recently stressed by a EULAR Consensus Committee (2). Current knowledge showed that pulses IV methylprednisolone (250 mg/day) are known to both saturate glucocorticoid receptors and assure a complete non genomic effect (3). <h3>Objectives</h3> To evaluate the effectiveness and safety of 250 mg IV methylprednisolone pulses in combination with immunosuppressive therapy in the treatment of lupus nephritis. <h3>Methods</h3> Twelve SLE patients (female 89%) aged from 21 to 70 years (median 33.5) and with disease duration ranging from 0.5 to 24 years (median 9.5), all of whom satisfied 2012 ACR criteria (4) for the classification of SLE, were evaluated in the study. All of them had active nephritis based on proteinuria &gt;0.5 g/24h and active urinary sediment or biopsy and 7 patients had impairment of renal function (i.e.,serum creatinine &gt;1.2 mg/dl). All were treated between 2012 to 2013 by EURO-Lupus nephritis regimen modified only in the range of 3 daily pulses of 250 mg IV methylprednisolone (instead of 750mg). Clinical response was evaluated at 3 and 6 months according to response criteria indicated in Euro-lupus nephritis trial (1) and the recently proposed outcome measures for lupus nephritis (5). Adverse events occurring from study inclusion to the last follow up visit were recorded. <h3>Results</h3> At enrollement patients presented an ECLAM score ranging from 1 to 10 (median 7), a SLEDAI score ranging from 3 to 18 (median 12); 24 hour proteinuria ranging from 0.675 to 14 g (median 2.86 g), serum creatinine ranging from 0.5 to 2.1 mg/dl (median 1 mg/dl). Three patients underwent a renal biopsy that pointed out a proliferative lupus glomerulonephritis (2 patients WHO class III-1 patient WHO class V). The table shows the changes detected at 3 and 6 months. No adverse events were registered. <h3>Conclusions</h3> Preliminary data of this ongoing study seem to indicate that pulse methylprednisolone (250mg/day) might be as effective as the used 750mg dosage as induction therapy for lupus nephritis. <h3>References</h3> Houssiau F A, et al. Arthritis Rheum 2002, 46: 2121–31 Duru N, et al. Ann Rheum Dis 2013;72:1905-13. Buttgereit F, et al. Arthritis Rheum 2004. 50: 3408–17 Petri M, et al. Arthritis Rheum 2012;64:2677-86. Wofsy D, et al. Arthritis Rheum 2013 65: 1586–91 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4227
Simultaneous, Multicolour Single Molecule Imaging of the Entire Human Epidermal Growth Factor Receptor (HER) Family in Live Breast Cancer Cells
Authors: L.C. Zanetti-Domingues, S. Webb, C. Tynan, D. Rolfe, M. Hirsch, B. Coles, S. Needham, S. Roberts, D. Clarke, M. Martin-Fernandez
Journal: Annals of Oncology (2013)
Cardiac and Acoustic Metastases in Relapsing Melanoma
Authors: Egesta Lopci, Lorenzo Monti, Luca Balzarini, Arturo Chiti
Journal: Clinical Nuclear Medicine (2013)

Herein we report the case of a 45-year-old woman with known history of malignant melanoma, complaining recent onset of bilateral hearing problems initially addressed to acoustic neuroma. Dedicated (18)F-FDG PET/CT and MR imaging documented the presence of 3 areas of pathologic uptake in the V-VII-VIII cranial nerves, other 2 in the neck and in the medullary sheath, and another unexpected lesion in the interventricular septum. All lesions showed intense (18)F-FDG uptake, high precontrast T1-weighted signal, contrast enhancement in T1-weighted sequences with gadolinium, and hypervascularization/high signal in T2-weighted images: these features were considered in keeping with diffused malignant melanoma metastatization.
Exercise Training and Nutritional Supplementation for Physical Frailty in Very Elderly People
Authors: Maria A. Fiatarone, Evelyn F. O'Neill, Nancy Doyle Ryan, Karen M. Clements, Guido R. Solares, Miriam E. Nelson, Susan B. Roberts, Joseph J. Kehayias, Lewis A. Lipsitz, William J. Evans
Journal: New England Journal of Medicine (1994)

Although disuse of skeletal muscle and undernutrition are often cited as potentially reversible causes of frailty in elderly people, the efficacy of interventions targeted specifically at these deficits has not been carefully studied.
Abstract 1606: Antitumor effects of vitamin D in a carcinogen-induced mouse model of lung cancer
Authors: Sarah A. Mazzilli, Mary E. Reid, Mukund Seshadri, Paul N. Bogner, Barbara A. Foster, Candace S. Johnson, Donald L. Trump
Journal: Cancer Research (2012)

Abstract Lung cancer accounts for the majority of cancer mortality in both men and women. It is critical to better understand the biology of lung cancer development as no preventive agents and few effective treatment options exist for lung cancer. Epidemiological studies indicate that low serum levels of 25(OH)D3 are associated with increased risk and poor prognosis of lung cancer. Calcitriol, the active metabolite of vitamin D, induces cell cycle arrest, apoptosis and differentiation in preclinical and clinical studies, has limited toxicity, and hence, is an attractive agent for chemoprevention. To investigate the preventive effects of vitamin D on lung squamous cell carcinoma (SCC), pre-clinical studies were conducted using a carcinogen-induced (CI) mouse model of lung SCC which uses N-nitroso-tris-chloroethylurea (NTCU) applied topically to the back of a SWR/J mouse twice weekly. Following ∼15 weeks of NTCU treatment, mice begin to develop bronchial epithelial hyperplasia and in time, progress through metaplasia, carcinoma in situ, and ultimately form lung SCC by approximately 35 to 40 weeks. We conducted a preliminary study investigating the effects of vitamin D on cancer progression in the CI model where animals received NTCU (80 mM/week). 12 week old female mice were randomized into one of three treatment groups: 1) vitamin D deficient diet (DD) (0IU D3 in the diet), 2) sufficient diet (SD) (2000IU/day D3 in the diet) and 3) SD with weekly intraperitoneal (IP) injections of calcitriol (80 ug/kg) (SD+D). Animals treated with NTCU on a DD, SD and SD+D had average serum 25(OH)D3 levels of 15, 70 and 75 nmol/L, respectively (normal range in mice is 70- 90 nmol/L). Preliminary histological evaluation at 12 weeks revealed bronchial epithelial hyperplasia in both the SD and SD+D groups. There were more advanced changes including hyperplasia, metaplasia and dysplasia in the DD mice. The histological evaluation of the DD mice at 24 weeks revealed even more advanced disease, in that most mice had developed lung SCC. The histological evaluation of the SD and SD+D groups at 24 weeks indicated the presence of bronchial epithelial hyperplasia, squamous metaplasia and dysplasia in all mice with some low level of carcinoma in situ. This study indicates that mice deficient in vitamin D develop disease at a more rapid rate suggesting that vitamin D status may play an important role in progression of lung SCC. Supported by NCCAM F31 AT006487 &amp; R01-CA-067267. 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 1606. doi:1538-7445.AM2012-1606
THU0111 Ra Patients with Inadequate Response to Oral MTX Maintain Satisfactory Disease Control and Durable Long-Term Response When Switched to SC MTX Monotherapy: Table 1
Authors: A. Hammond, M. Batley
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Methotrexate (MTX) is the cornerstone of rheumatoid arthritis (RA) therapy, but many patients do not achieve adequate response to oral therapy for reasons of tolerability or efficacy.<sup>1,2</sup> Subcutaneous (SC) MTX should be considered for RA patients who have an unsatisfactory response to oral MTX.<sup>3</sup> <h3>Objectives</h3> In this analysis, RA patients switched from oral MTX to SC MTX monotherapy were evaluated to understand durability of response and disease control. <h3>Methods</h3> A retrospective analysis of RA patient data collected from 2003 to 2011 at a single site in the United Kingdom<sup>4</sup> was performed. Per institutional practice, incremental oral MTX dose increase was followed by a switch to SC MTX. Folic acid (5-15 mg) was given 1 day after SC MTX treatment as a matter of routine practice. Mean duration on SC MTX monotherapy following switch from oral MTX was documented via patient record review. <h3>Results</h3> One hundred twelve RA patients were eligible for analysis. Mean age was 60.9 years (range, 26-83 y), and mean disease duration was 8.3 years (range, 0.5-46 y). 49 (44%) patients with an inadequate response to oral MTX for reasons of tolerability or efficacy were switched to SC MTX monotherapy and included in this analysis (Table). Twenty patients (41%) switched from oral MTX to SC MTX for reasons of tolerability. Among these patients, mean DAS28 improved by 1.05, patients remained on SC MTX monotherapy for a mean of 28.6 months before additional treatment was added, and 40% (8) achieved low disease activity (LDA) of DAS28 ≤3.2. Twenty-nine patients (59%) switched for reasons of efficacy. Among these patients, mean DAS28 scores improved by 1.26, patients remained on SC MTX monotherapy for a mean of 34.58 months before addition of other therapies, and 24% (7) achieved LDA. <h3>Conclusions</h3> In this single-center analysis, RA patients with an inadequate response to oral MTX for reasons of efficacy and/or tolerability maintained satisfactory disease control and durable, long-term response when switched to SC MTX monotherapy. <h3>References</h3> Salliot C, van der Heijde D. Long-term safety of methotrexate monotherapy in patients with rheumatoid arthritis: a systematic literature research. Ann Rheum Dis. 2009;68:1100-1104. Visser K, van der Heijde D. Optimal dosage and route of administration of methotrexate in rheumatoid arthritis: a systematic review of the literature. Ann Rheum Dis. 2009;68:1094-1099. Hameed B, Jones H. Subcutaneous methotrexate is well tolerated and superior to oral methotrexate in the treatment of rheumatoid arthritis. Int J Rheum Dis. 2010;13:e83-e84. Liakos A, et al. Ann Rheum Dis. 2012;71:672. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2353
SAT0058 Slug is induced by benzo(a)pyrene and egf through PI3K/AKT/MTOR pathway and is closely involved in the regulation of the invasive properties of FLS in rheumatoid arthritis
Authors: J. Lee, J.W. Hwang, J.W. Noh, E.-J. Park, E.-K. Bae, J.K. Ahn, J. Kim, H.-S. Cha, E.-M. Koh
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Slug, a Snail family of zinc finger transcription factor, plays a critical role in tumor proliferation, invasion and metastasis. We have previously shown that Slug is overexpressed in RA synovial tissue and suppression of Slug facilitates apoptosis of RA FLS. However, the precise mechanism through which Slug is induced in RA FLS remains unclear. Smoking is an important environmental risk factor for RA and influences RA disease susceptibility and severity. Benzo(a)pyrene (BaP) is a polycyclic aromatic hydrocarbon found in cigarette smoke. BaP can be metabolized to active compounds that induce the production of reactive oxygen species. The effect of Bap on Slug expression in RA FLS has not been studied thus far. <h3>Objectives</h3> The present study was undertaken to investigate the biological effects of BaP on the expression of Slug, signaling pathway through which Slug is expressed, and the effect of BaP/Slug on the invasive properties of RA FLS. <h3>Methods</h3> Expression of Slug was measured by real-time PCR following stimulation of FLS with different concentrations of BaP, EGF, H<sub>2</sub>O<sub>2</sub>, TGF-β, and TNF-α (n=7, each). Phosphorylation of the key enzymes in the signal transduction pathway was analyzed by Western blot. Inhibitors targeting the PI3K/Akt/mTOR pathway were used to confirm critical signaling pathway for Slug expression (n=7). An in vitro cell invasion assay was performed using RA FLS treated with Slug siRNA or with control siRNA (n=4). <h3>Results</h3> Slug expression was significantly increased following treatment with BaP (4μM, p=0.0014), EGF (100ng/ml, p=0.027) and H<sub>2</sub>O<sub>2</sub> (0.25mM, p=0.029), but not with TGF-β and TNF-α. Stimulation with BaP and EGF induced phosphorylation of Akt kinase activity, but no significant change was observed in ERK, JNK and p38 activity. Slug mRNA expression by BaP and EGF decreased significantly following treatment with PI3K/Akt/mTOR inhibitors (p=0.0256, p=0.0193, respectively). Slug siRNA treatment induced a significant reduction in the invasive function of FLS compared to those treated with control siRNA (p=0.029). In addition, stimulation with BaP increased invasive function of FLS, but was not statistically significant (p=0.057). Bap stimulation of Slug siRNA treated FLS did not induce increase in the invasive function of FLS. <h3>Conclusions</h3> Our data show that BaP, one of major toxic components in cigarette smoke, induce Slug expression in RA FLS through PI3K/Akt/mTOR pathway, and may regulate invasive properties of RA FLS. This mechanism may provide a novel explanation for the increased RA susceptibility and severe clinical phenotype in those who smoke. <h3>Disclosure of Interest</h3> None Declared
Multifactorial Index of Cardiac Risk in Noncardiac Surgical Procedures
Authors: Lee Goldman, Debra L. Caldera, Samuel R. Nussbaum, Frederick S. Southwick, Donald Krogstad, Barbara Murray, Donald S. Burke, Terrence A. O'Malley, Allan H. Goroll, Charles H. Caplan, James Nolan, Blase Carabello, Eve E. Slater
Journal: New England Journal of Medicine (1977)

To determine which preoperative factors might affect the development of cardiac complications after major noncardiac operations, we prospectively studied 1001 patients over 40 years of age. By multivariate discriminant analysis, we identified nine independent significant correlates of life-threatening and fatal cardiac complications: preoperative third heart sound or jugular venous distention; myocardial infarction in the preceding six months; more than five premature ventricular contractions per minute documented at any time before operation; rhythm other than sinus or presence of premature atrial contractions on preoperative electrocardiogram; age over 70 years; intraperitoneal, intrathoracic or aortic operation; emergency operation; important valvular aortic stenosis; and poor general medical condition. Patients could be separated into four classes of significantly different risk. Ten of the 19 postoperative cardiac fatalities occurred in the 18 patients at highest risk. If validated by prospective application, the multifactorial index may allow preoperative estimation of cardiac risk independent of direct surgical risk.
PWE-063 Evaluation Of a Previously Described Scoring System for Predicting Complications Post Ercp
Authors: M C Donnelly, V A Watt, J S Leeds
Journal: Gut (2013)

<h3>Introduction</h3> Endoscopic retrograde cholangiopancreatography (ERCP) is widely performed for the management of biliary and pancreatic duct disorders. Despite this, ERCP is associated with a significant complication rate, with the literature reporting rates of post-procedural pancreatitis of 1–5%, cholangitis in 1–5% and haemorrhage in 1%. A previous study (Jeurnink <i>et al</i> 2011<sup>1</sup>) described a prognostic model for predicting those patients at greater risk of developing post ERCP complications, and identifying those who may be safely discharged shortly after ERCP. The aim of this study was to validate this scoring system in an external cohort to assess whether it can be used in general clinical practise. <h3>Methods</h3> Details of all patients undergoing ERCP over the 22 month period from May 2010 to February 2012 were recorded on an institutionally approved database. Electronic records were subsequently accessed to identify post ERCP complications within 30 days of procedure. The predictive score as described was retrospectively calculated and applied to all patients, with a score &gt; 3 being considered high risk. Sensitivity, specificity, negative and positive predictive values were then calculated. <h3>Results</h3> 697 patients (409 females, mean age 64, mean ASA grade 2.35) underwent ERCP during the study period. The overall complication rate was 9.0% (63/697); cholangitis 2.3% (n = 16), pancreatitis 2.1% (n = 15), bleeding 1.6% (n = 11), perforation 1.3% (n = 9) and miscellaneous in 1.7% (n = 12). The mortality rate was 0.4% in our cohort (n = 3). 681/697 (97.7%) had a predictive score &lt; 4 but ERCP grade 1/2/3 was 531/149/17 respectively. Of those with a predictive score ≥4, 12.5% (n = 2/16) developed a post-ERCP complication (both severe pancreatitis) versus 8.4% (n = 57/681) with a score &lt; 4 (p = ns). Using the predictive score gave a sensitivity of 3.4%, specificity of 97.8%, positive predictive value of 13% and a negative predictive value of 92%. <h3>Conclusion</h3> The predictive scoring system as previously described does not accurately stratify patients into high or low risk groups or predict post-ERCP complications in our cohort. This may be due to case mix in the original cohort leading to lack of generalisation. Further work is needed to formulate a clinically applicable scoring system which has higher accuracy. <h3>Disclosure of Interest</h3> None Declared. <h3>Reference</h3> Jeurnink SM, Siersema PD, Steyerberg EW, Dees J, Poley JW, Haringsma J, Kuipers EJ. Predictors of complications after endoscopic retrograde cholangiopacreatography: a prognostic model for early discharge. Surg Endosc (2011) 25: 2892–2900