tbuckley/cabot-search huggingface dataset:
Abstract 3325: Cancer stem cell like properties of 5-fluorouracil resistant Panc-1 cell
Authors: Motoko Izumiya, Hajime Higuchi, Ayano Kabashima, Toru Igarashi, Shoko Nakamura, Shinsuke Funakoshi, Masayuki Adachi, Hiromasa Takaishi, Toshifumi Hibi
Journal: Cancer Research (2010)

Abstract Cancer stem cells (CSCs), a small fraction of tumor-initiating cells, are known to be resistant to chemotherapy-induced apoptosis. CSCs are considered to be responsible for self-renewal/differentiation, invasion, and metastasis of malignant tumor. We have previously reported that pancreatic cancer derived side population (SP) cells, a cancer stem cell enriched fraction, were more resistant to chemotherapeutic agents and more likely to cause epithelial-to-mesenchymal transition (EMT) compare to major population (MP) cells. Therefore, we formulated the HYPOTHESIS that 5-fuluorouracil (5-FU) resistant population cells are enriched with CSCs. The AIM of this study is to evaluate whether apoptosis-resistant cancer cells have CSC-like properties, i.e., self-renewal, local invasion and EMT. METHODS: Seventy to eighty percent confluent pancreatic cancer cells, PANC-1, were incubated in the presence of 5-FU (30mg/ml) for 24 hours, and further incubated for one to five weeks without 5-FU. To assess the capacity of self-renewing, cells were planted using a method for anchorage-independent culturing to form spheroids. EMT was induced with TGF-beta (7.5 ng/ml, for 3 days), then evaluated mRNA expression by real time PCR for E-cadherin, Snail, and vimentin. E-cadherin protein level was also examined for immunoblot analysis. Activity of local invasion was analyzed by Matrigel invasion assay. To evaluate tumorigenicity, 5-FU resistant cells were injected into NOD/SCID mice. RESULTS: 5-FU induced significant apoptosis in PANC-1 cells, reducing the number of surviving cells to less than one percent. The survived cells showed a colony-forming activity as they started to re-proliferate at four weeks after 5-FU removal. There was a group of cells among the 5-FU resistant surviving cells, that gradually regains sensitivity to 5-FU by re-plating. The frequency of cells that were capable of initiating spheres was higher in 5-FU resistant cells and they over expressed stem cell marker genes, Oct 4 and Nanog. Incubation with TGF-beta induced EMT-associated gene alterations. These alterations were greater in 5-FU resistant surviving cells as compared to untreated cells. Matrigel invasion activity of apoptosis-resistant PANC-1 cells was greater by seven fold than controlled cells. In addition, in vivo tumor experiments showed 5-FU resistant cells to be more tumorigenic than conventional Panc-1 cells. In CONCLUSION, apoptosis-resistant cancer cells have CSC-like properties, i.e., initiating sphere formation, expressing stem cell genes, and respond to EMT stimulation. 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 3325.
Treatment of Cryptococcal Meningitis with Combination Amphotericin B and Flucytosine for Four as Compared with Six Weeks
Authors: William E. Dismukes, Gretchen Cloud, Harry A. Gallis, Thomas M. Kerkering, Gerald Medoff, Philip C. Craven, Lisa G. Kaplowitz, John F. Fisher, Clark R. Gregg, Cynthia A. Bowles, Smith Shadomy, Alan M. Stamm, Robert B. Diasio, Leo Kaufman, Seng-jaw Soong, William C. Blackwelder
Journal: New England Journal of Medicine (1987)

One hundred ninety-four patients with cryptococcal meningitis were enrolled in a multicenter, prospective, randomized clinical trial to compare the efficacy and toxicity of four as compared with six weeks of combination amphotericin B and flucytosine therapy. Among 91 patients who met preestablished criteria for randomization, cure or improvement was noted in 75 percent of those treated for four weeks and in 85 percent of those treated for six weeks. The estimated relapse rate for the four-week regimen was higher — 27 as compared with 16 percent — whereas the incidence of toxic effects for the two regimens was similar — 44 as compared with 43 percent. Among 23 transplant recipients, 4 of 5 treated for four weeks relapsed, leading to the decision to treat the rest of the group for six weeks. Only 3 of the 18 treated for six weeks relapsed. In a third group of 80 patients, the protocol was not followed during the initial four weeks, and these patients were not randomized. Thirty-eight died or relapsed. Multifactorial analysis of pretreatment factors for all 194 patients identified three significant predictors (P<0.05) of a favorable response: headache as a symptom, normal mental status, and a cerebrospinal fluid white-cell count above 20 per cubic millimeter. These and other findings in this study are consistent with the view that the four-week regimen should be reserved for patients who have meningitis without neurologic complications, underlying disease, or immunosuppressive therapy; a pretreatment cerebrospinal fluid white-cell count above 20 per cubic millimeter and a serum cryptococcal antigen titer below 1:32; and at four weeks of therapy, a negative cerebrospinal fluid India ink preparation and serum and cerebrospinal fluid cryptococcal-antigen titers below 1:8. Patients who do not meet these criteria should receive at least six weeks of therapy. (N Engl J Med 1987; 317:334–41.)
COMPARISONS BETWEEN ECHO-DOPPLER WAVE PATTERN AND AGASTON SCORE FOR PREDICTING FUTURE PROGNOSIS IN PATIENTS WITH ASYMPTOMATIC AORTIC STENOSIS
Authors: Keisuke Minami, Masaki Izumo, Kengo Suzuki, Kanako Teramoto, Maya Tsukahara, Yukio Sato, Shingo Kuwata, Ryo Kamijima, Kei Mizukoshi, Manabu Takai, Seisyou Kou, Akio Hayashi, Yoshihiro Akashi
Journal: Journal of the American College of Cardiology (2016)
FRI0269 Microthrombotic renal vascular lesions are associated to increased renal inflammatory infiltration in a mouse model of lupus nephritis
Authors: E. Gonzalo, O. Toldos, S. Pérez-Yagüe, G. Criado, D. F. Barber, J. L. Pablos, M. Galindo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Presence of vascular microthrombotic lesions in lupus nephritis (LN), with or without antiphospholipid antibodies (aPL), may relate to worse renal outcome. Whether microthrombotic lesions are a consequence of renal inflammation or independently contribute to renal damage is unclear. <h3>Objectives</h3> The aim of this study was to analyze renal vascular involvement in MRL/lpr mice and its association to the degree of renal inflammation, presence of aPL and renal function. <h3>Methods</h3> We used 12-20-week old female MRL/lpr mice with nephritic lesions (n=41). The pattern of renal vascular disease, acute and chronic glomerular and tubulointerstitial lesions were analyzed by using H&amp;E and PAS staining. Immunohistochemistry (IHC) techniques were used to detect CD41, fibrinogen (FGN), complement (C3) and macrophages. Expression of CD41 was detected indicating the presence of platelet thrombi. Expression of FGN, C3 and intraglomerular macrophagic infiltration (Mac-2) were quantified using Image J software. Periglomerular macrophagic F4/80 was quantified as the percentage of positive glomeruli. Renal function was assessed by measuring levels of serum creatinine (Cr<sub>s</sub>) and proteinuria. Serum levels of a-dsDNA and anticardiolipin (aCL) antibodies were quantified by ELISA. Association between categorical variables was tested by the X<sup>2</sup> test. For continuous variables, comparisons were carried out using <i>t</i>-test. A Spearman’s rank test was used for correlations among different parameters. <i>P</i>&lt;0.05 was considered significant. Statistical analysis was performed using advanced SPSS software version 11. <h3>Results</h3> Mice with microthrombotic renal vascular lesions showed a greater degree of periglomerular macrophage infiltration (55.4%vs34.9%; p=0.002). All mice had detectable a-dsDNA or aCL IgG, but no relationship between both autoantibody titer and TMA or CD41+ was found. Proteinuria was positively correlated to the proportion of sclerotic glomeruli (r=0.4; p=0.01), glomerular macrophage infiltration (r=0.46; p=0.004) and was higher in mice with diffuse proliferative glomerular lesions (340.8vs110.8; p=0.02). Correlation between renal vascular lesions and complement deposits, level of proteinuria or Crs was not found. <h3>Conclusions</h3> Presence of microthrombotic renal vascular lesions is associated to a higher degree of macrophage infiltration in lpr model of LN. Although a direct impact on proteinuria or renal function could not be demonstrated this model allows analyzing the impact of anti-thrombotic and anti-inflammatory interventions on renal inflammation. <b>Disclosure of Interest</b>: None Declared
SAT0445 Respective contribution of musculoskeletal and other chronic disorders to disability in france: Results from the national disability-health survey
Authors: C. Palazzo, J.-F. Ravaud, L. Trinquart, M. Dalichampt, P. Ravaud, S. Poiraudeau
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Representative national data on disability are becoming increasingly important in helping policymakers decide on public health strategies. <h3>Objectives</h3> We assessed the respective contribution of chronic health conditions, including musculoskeletal diseases, to disability for three age groups (≤40, 40–65, and &gt;65 years old) using data from the 2008–2009 Disability-Health Survey in France. <h3>Methods</h3> Data on 12 chronic conditions and on disability for 24 682 adults living in householdswere extracted from the Disability-Health Survey results. A weighting factor was applied to obtain representative estimates for the French population.We considered three disability categories: functional disability which was defined as at least one restriction in activities of daily living (ADL), severe disability as the inability to perform at least one ADL alone, and self-reported disability as a general feeling of being disabled. To account for co-morbidities, we assessed the contribution of each chronic disorder to disability by using the average attributable fraction (AAF). <h3>Results</h3> Weestimatedthat 38.8 million people in France (81.7% [80.9;82.6]) had a chronic condition (13.7 millions (28.7% [27.9;29.5]) reported musculoskeletal diseases): 14.3% [14.0;14.6] considered themselves disabled, 4.6% [4.4;4.9] were restricted in ADL and 1.7% [1.5;1.8] were severely disabled.Musculoskeletal disorders contributed the most to self-reported disability (AAF 15.4%) and had the second largest impact on functional disability (AAF 16.4% versus 17.4% for neurological conditions). Their contribution to severe disability was almost nil (AAF 0.0%). These estimates vary according to the age group. Psychiatric diseases contributed the most to disability categories for patients 40 years old and younger (AAF 23.8%–40.3%). <h3>Conclusions</h3> Musculoskeletal, neurological and cardiovascular chronic disorders mainly contribute to disability in France. Musculoskeletal diseases have the largest impact on self-reported disability. Results vary according to the age group. These findings should help policymakers define priorities for health-service delivery in France and perhaps other developed countries. <h3>Disclosure of Interest</h3> C. Palazzo Grant/Research support from: We received grant from Pfizer France, which had no role in study design, data collection and analysis, J.-F. Ravaud: None Declared, L. Trinquart: None Declared, M. Dalichampt: None Declared, P. Ravaud: None Declared, S. Poiraudeau Consultant for: received fees from Pfizer for consultancy.
Increased Activity in Benign Phyllodes Tumor on Tc-99m MDP Scintimammography
Authors: N Katayama, Y Inoue, T Ichikawa, M Harada, T Itoh, K Shimoyamada, M Ikeda, Y Tsukune
Journal: Clinical Nuclear Medicine (2000)

Phyllodes tumor is an uncommon fibroepithelial breast tumor. The authors describe a patient with a benign phyllodes tumor of the breast who underwent Tc-99m MDP scintimammography. Definitely increased activity at the site corresponding to the tumor was observed on images obtained soon after the injection of Tc-99m MDP. The mass was excised, and pathologic analysis showed it to be a benign phyllodes tumor. The case reported indicates that benign phyllodes tumor is a possible cause of false-positive findings on scintimammography with Tc-99m MDP.
TCT-383 Long-term Vascular Response to Biodegradable Polymer Biolimus-Eluting Stents in Comparison With Durable Polymer Sirolimus-Eluting Stents and Bare-Metal Stents: Five-year Follow-up Optical Coherence Tomography Study
Authors: Shoichi Kuramitsu, Shinjo Sonoda, Takenori Domei, Shinichi Shirai, Kenji Ando
Journal: Journal of the American College of Cardiology (2014)
Abstract SY04-02: Reaching escape velocity: Using lineage tracing to study EMT and dissemination in pancreatic cancer
Authors: Ben Z. Stanger
Journal: Cancer Research (2012)

Abstract Metastastic spread has been difficult to study because it involves a series of rare events that are difficult to observe in vivo. To capture such events, we have employed lineage tracing - a technique which allows cells to be tagged and tracked - and applied it to an autochthonous mouse model of pancreatic cancer. Using this approach, found that pancreas-derived cells entered the circulation at the PanIN-stage, prior to the presence of a histologically recognizable tumor. Moreover, invasive behavior was almost universally associated with epithelial-to-mesenchymal transition (EMT), and bloodstream entry was associated with a “cancer stem cell” phenotype. These observations demonstrate that cellular dissemination in pancreatic cancer can occur at a very early stage of tumor progression. 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 SY04-02. doi:1538-7445.AM2012-SY04-02
Abstract 4460: Aromatase inhibition by active tamoxifen metabolites
Authors: Wenjie J. Lu, David A. Flockhart
Journal: Cancer Research (2011)

Abstract Introduction: The mechanism of tamoxifen action in the treatment of breast cancer is believed to be via active metabolites that act as potent antagonists at the estrogen receptors. Despite this, few data have been published that relate the concentrations of these metabolites to their expected clinical effects. Since anti-estrogenic clinical effects may be brought about not only by estrogen antagonism but also by reduced estrogen concentrations, we tested the direct effects of tamoxifen and its active metabolites on aromatase activity. Methods: The activity of recombinant human aromatase was measured by following the generation of fluorescent metabolite from 7-methoxy-4-trifluoromethylcoumarin (MFC) in microsomal incubations in the presence and absence of multiple concentrations of tamoxifen, endoxifen, N-desmethyl-tamoxifen and 4-hydroxy-tamoxifen. Inhibition of aromatase was determined at enzyme concentrations set at 7.5 nM by measuring the percentage of enzyme activity remaining. Results: With MFC concentrations at the Km (25 µM), the IC50s for endoxifen and N-desmethyl-tamoxifen were 6.1 µM and 20.7 µM respectively. At concentrations up to 50 µM, no appreciable inhibition by tamoxifen or 4-hydroxy-tamoxifen was observed. Detailed characterization of inhibition by endoxifen and N-desmethyl-tamoxifen across a range of substrate concentrations demonstrated non-competitive kinetics for both inhibitors. The Ki values for endoxifen and N-desmethyl-tamoxifen were 4.0 µM and 15.9 µM respectively. Preincubation of these tamoxifen metabolites with aromatase did not demonstrate any irreversible effect on enzyme activity. Discussion: Among tamoxifen and its three major metabolites, only endoxifen and N-desmethyl-tamoxifen were found to be potent inhibitors of aromatase. This enzyme is the major source of estrogen in humans, and changes in its activity may thus alter estrogen-regulated physiology. Inhibition by these tamoxifen metabolites may contribute to changes in serum and tissue estrogen concentrations, and may explain in part the variability in bone density, serum lipid concentration, severity of musculoskeletal pain and breast cancer recurrence observed in patients taking tamoxifen. Relationships between tamoxifen metabolite concentrations and clinical outcomes may be complex, and mechanisms that underlie the multiple clinical effects of tamoxifen include the possibility of aromatase inhibition by endoxifen and N-desmethyl-tamoxifen. 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 4460. doi:10.1158/1538-7445.AM2011-4460
HIGH-RESOLUTION END-SYSTOLIC MYOCARDIAL PERFUSION MRI ENABLES RELIABLE DETECTION OF SUBENDOCARDIAL ISCHEMIA IN THE ABSENCE OF OBSTRUCTIVE CORONARY DISEASE
Authors: Behzad Sharif, Daniel Berman, Rohan Dharmakumar, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2016)
An Index Predicting Relapse and Need for Hospitalization in Patients with Acute Bronchial Asthma
Authors: Margaret A. Fischl, Arthur Pitchenik, Laurence B. Gardner
Journal: New England Journal of Medicine (1981)

In an attempt to define guidelines for the assessment of acute asthma, we evaluated 205 patients who presented to the emergency room for treatment of asthma. Of the 205, 120 were successfully treated and discharged from the emergency room, 45 were hospitalized, and 40 were treated and discharged from the emergency room but had relapses within 10 days. A predictive index using a combination of presenting factors was developed: pulse rate ≥120 per minute, respiratory rate ≥30 per minute, pulsus paradoxus ≥18 mm Hg, peak expiratory flow rate ≤120 liters per minute, moderate to severe dyspnea, accessory-muscle use, and wheezing. The index ranged from 0 to 7, increasing with the severity of symptoms. The index scores of the relapse group (4.9±1.0) and the admitted group (5.1±1.0) were both significantly different (P<0.001) from that of the successfully treated group (1.6±1.2). An index of 4 or higher was 95 per cent accurate in predicting the risk of relapse and 96 per cent accurate in predicting the need for hospitalizaron. (N Engl J Med. 1981; 305:783–9.)
P638PERK- a potential molecular regulator of calcium homeostasis related with arrhythmia in diabetic cardiomyopathy
Authors: Z Liu, JK Wang, HT Zhu, N Zhao, C Qiu
Journal: Cardiovascular Research (2014)

Purpose: Arrhythmia is often found a complication of diabetes, which takes major responsibility of malignant ventricular arrhythmias and even sudden cardiac death (SCD) in patients with diabetic cardiomyopathy (DbCM). In our previous study, rats model of DbCM was established and verified by occurrence of diabetes and impaired cardiac function. Increased incidence of ventricular arrhythmia was observed in these rats, which was accompanied by intensified endoplasmic reticulum stress (ERS) in cardiac tissue. ERS was suggested related with calcium homeostasis, whose fluctuation may further induce arrhythmia by initiating cellular electrophysiological changes. Though previous results indicated ERS might play a role in ventricular arrhythmia in DbCM, much further investigations are still need to explore the mechanisms. This current study was aimed to preliminarily reveal the possible molecular regulators in this process. Methods: DbCM rat model was induced by intraperitoneal injection of streptozotocin and testified by cardiac function determination. Occurrence of ventricular arrhythmia was observed after rats received 4-PBA administration. After isolated from hearts of neonatal rats, myocytes were treated by siRNA to knockdown the expressions of three transducers of ERS, namely protein kinase RNA-like ER kinase (PERK), inositol- requiring enzyme-1 (IRE1) and activating transcription factor-6 (ATF6) respectively. Myocytes were then treated by high- glucose incubation, and cytoplasmic calcium uptake and release were evaluated by Fura2-AM staining under a fluorescence microscope. Enzymatic activity of calcineurin and unclear translocation of nuclear factor of activated T cells c1 (NFATc1) were also examined in myocytes. Results: 1. After treated by 4-PBA, an ERS specific inhibitor, the occurrence of ventricular arrhythmia was decreased significantly in DbCM rats. 2. 4-PBA treatment decreased both cytoplasmic calcium uptake and ER calcium release in high- glucose incubated myocytes. 3. PERK knockdown stabilized calcium dynamics rather than IRE-1 or ATF-6 knockdown in high- glucose incubated myocytes. 4. Both calcineurin activity and NFATc1 tanslocation were increased by inhibited by PERK knockdown myocytes in high- glucose incubated myocytes. Conclusions: 1. ERS induces ventricular arrhythmia in DbCM, probably via affecting calcium dynamics in myocytes; 2. PERK/calcinerin/NFAT signaling pathway may act an important role in introducing fluctuation of calcium homeostasis in DbCM.
Erratum: NRF2 regulates serine biosynthesis in non–small cell lung cancer
Authors: Gina M DeNicola, Pei-Hsuan Chen, Edouard Mullarky, Jessica A Sudderth, Zeping Hu, David Wu, Hao Tang, Yang Xie, John M Asara, Kenneth E Huffman, Ignacio I Wistuba, John D Minna, Ralph J DeBerardinis, Lewis C Cantley
Journal: Nature Genetics (2016)