tbuckley/cabot-search huggingface dataset:
Abstract 293: TGF-b regulates Par-4 expression through XIAP in ovarian and endometrial cancers.
Authors: Francois Fabi, Sophie Parent, Valérie Leblanc, Eric Asselin
Journal: Cancer Research (2013)

Abstract The lethality of gynecological malignancies can be explained by their propensity to develop chemioresistance and metastases. The loss of apoptotic pathways is one of the major underlying mechanisms by which tumors become resistant to treatments. This loss can be explained by the silencing of pro-apoptotic proteins that would normally contrive the cell into suicide. Par-4 is a tumor suppresor protein that is widely expressed but only functionally silenced in most endometrial cancer. This protein presents the unique ability to induce apoptosis selectively in cancer cells. We have recently demonstrated that Par-4 is a substrate of caspase-3 and the resulting cleaved fragment retains its apoptotic-inducing capabilities. We have also evidenced that TGF-β, a known instigator of EMT, regulates the invasiveness of endometrial cancer cells and Par-4 expression. TGF-β has also been shown to increase the expression of XIAP, an important promoter of cell survival and invasiveness in endometrial cancer. In this study, we have investigated the effect of TGF-ß and XIAP on Par-4 expression in ovarian and endometrial cancer. We have performed rescue experiment in which MEFs cells from XIAP KO mice were cultured and transfected with either an empty plasmid, a wild-type XIAP plasmid or a XIAP mutated RING domain plasmid. We have then submitted these cells to cisplatin treatment. In the empty vector transfectants, we have found that the absence of XIAP results in Par-4 cleavage, increased cleaved caspase-3 and cleaved PARP. The rescue of XIAP inhibited the apoptotic machinery and Par-4 cleavage thus resulting in increased chemoresistance. This effect was reversed using the mutated XIAP plasmid. We have also treated endometrial cancer cells (HeLa, KLE) with TGF-ß3 and observed an higher expression of EMT markers such as Snail, Vimentin and N-Cadherin; Par-4 was also upregulated by TGF-ß3. Finally, we have overexpressed ovarian A2780 cancer cells with Par-4 plasmid, which resulted in the upregulation of Snail and Vimentin. We confirmed these results using Par-4 siRNA and found that Snail and Vimentin expression were reduced. Altogether, results of the present study shed new light in the underlying mechanisms of Par-4 regulation and apoptosis induction. The assembled data also suggests that TGF-β plays a cardinal role in the regulation of Par-4 expression, which regulates EMT in gynecological cancers. Citation Format: Francois Fabi, Sophie Parent, Valérie Leblanc, Eric Asselin. TGF-b regulates Par-4 expression through XIAP in ovarian and endometrial cancers. [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 293. doi:10.1158/1538-7445.AM2013-293
Suppression of alveolar macrophage membrane receptor-mediated phagocytosis by model and actual particle-adsorbate complexes. Initial contact with the alveolar macrophage membrane.
Authors: G J Jakab, T H Risby, S S Sehnert, R R Hmieleski, J E Farrington
Journal: Environmental Health Perspectives (1990)

Alveolar macrophages were treated with carbon blacks and adsorbates in order to evaluate the biologic effect of adsorbate, adsorbent and adsorbate-adsorbent complexes. Their capacity to phagocytize a subsequent challenge via the Fc-membrane receptor was quantified. Phagocytosis was suppressed in a dose-related manner with increasing concentrations of both carbon blacks and adsorbates. Carbon black N339 covered with 0.5 monolayers of the adsorbates suppressed phagocytosis more than N339 without the adsorbates. Increasing the adsorbate acrolein coverage from 0.5 to greater than 2.0 monolayers suppressed phagocytosis in a dose-related manner. Finally, samples of diesel particulate matter collected from an engine operated on a pure hydrocarbon fuel with various oxidizers, air (PSU #1) and an oxidizer free of nitrogen (N-free) were tested. Treatment of the macrophages with PSU #1 had a negligible effect on phagocytosis whereas the N-free sample suppressed phagocytosis in a dose-related manner. The data show that alveolar macrophage Fc-receptor-mediated phagocytosis is affected by: carbon black and adsorbate identity and concentration, coverage of the carbon black with adsorbates, and the oxidizer used in the generation of particles emitted by a diesel engine.
Food-poisoning due to Cl. welchii
Authors: J. G. Collee
Journal: BMJ (1954)

THE report of the Medical Research Council for the year 1951-2 records that one of the most recent additions to the list of recognized causative organisms of food-poisoning is a heat-resistant variant of Cl. welchii. The present paper describes an outbreak of food-poisoning in an army camp in which there is evidence to presume that Cl. welchii was responsible. In a comprehensive study of clostridial food-poisoning, Hobbs, Smith, Oakley, Warrack and Cruickshank (1953) pointed out that, as early as 1895, Klein isolated Cl. welchii from stools obtained in two epidemics of diarrhrea, but that it was not until the last decade that evidence has been forthcoming to incriminate the organism more convincingly as a possible cause of much hitherto non-specific food-poisoning. They note, for example, that no adequate cause was found in 36 per cent. of the 2,431 outbreaks of food-poisoning recorded for 1949. Smither (1953) investigated 90 unselected cases of gastro-enteritis in general practice, and he could isolate no recognized pathogens from 71 of his patients in this series. He was convinced that a heat-resistant staphylococcal enterotoxin was the commonest cause of mild gastro-enteritis, but he stated that no special bacteriological techniques were employed in his investigations and it appears that his specimens were not examined for Cl. welchii.
A phase I study of palifosfamide in combination with doxorubicin: Safety and preliminary efficacy
Authors: L. H. Camacho, S. P. Chawla, V. Chua, G. Abbadessa, P. B. Komarnitsky, J. Lewis
Journal: Journal of Clinical Oncology (2009)

10577 Background: Palifosfamide, a bi-functional DNA alkylator is the active metabolite of ifosfamide (IFOS), that lacks the toxicity associated with non-active IFOS metabolites and does not require activation. Recent phase II data shows single agent activity in advanced refractory sarcoma. Marked preclinical synergistic efficacy of palifosfamide in combination with doxorubicin provides a strong rationale for clinical evaluation of this combination regimen. Methods: Eligible subjects with advanced refractory tumors were included if no standard therapy exists and if doxorubicin treatment is medically acceptable. Palifosfamide was administered on days 1 - 3 of a 21 day cycle, starting dose of 100 mg/m 2 . Doxorubicin was administered on day 1 of 21 day cycle, starting dose of 60 mg/m 2 . Dose was escalated up to MTD or palifosfamide 150 mg/mg 2 , doxorubicin 75 mg/m 2 . Pharmacokinetics (PK) for palifosfamide were determined and compared to those obtained in murine PK/efficacy studies. Results: 13 patients with advanced tumors (8 with soft tissue sarcoma - STS, 5 with SCLC, neuroendocrine and osteosarcoma) have been treated with 8 patients still on treatment. All had ECOG PS &lt;2, median age was 58, and 3 had received prior IFOS. With 51 cycles administered, the combination has been well tolerated, with no dose-limiting toxicities reported. Pts did not receive Mesna or hydration. Study-related Grade 3/4 adverse events include neutropenia and thrombocytopenia. PK evaluation indicates that palifosfamide exposure and Cmax at clinically well-tolerated doses are comparable with those in murine models resulting in marked synergy with doxorubicin. Efficacy in 12 evaluable pts: 3/12 PRs, (2/8 PRs for STS); PFS median duration 20 weeks and ongoing. Conclusions: Palifosfamide in combination with doxorubicin is easy to administer, and has been very well tolerated with no encephalopathy, no hemorrhagic cystitis and no renal toxicity. Early efficacy data has prompted an ongoing randomized phase II study in STS comparing doxorubicin 75 mg/m 2 to palifosfamide 150 mg/m 2 + doxorubicin 75 mg/m 2 . [Table: see text]
Sodium Diuresis after Relief of Obstructive Uropathy
Authors: Francis P. Muldowney, G. J. Duffy, D. G. Kelly, F. A. Duff, C. Harrington, R. Freaney
Journal: New England Journal of Medicine (1966)

STRIKING urinary losses of water and sodium after relief of chronic urinary-tract obstruction were first recorded by Wilson, Riseman and Moyer.1 Further cases were reported by Parsons2 and by Bricker et al.3 Many of these patients appeared to lose sodium and water at such a rate that a clinical state of dehydration and shock resulted. Parenteral replacement of saline solutions was followed by clinical improvement.The magnitude and duration of this apparently catastrophic sodium loss cannot be assessed from the available data since these are necessarily complicated by intravenous or oral sodium replacement therapy. In addition, there is no available . . .
Use of Sulfadiazine in Presence of Hematuria
Authors: Joseph H. Nicholson
Journal: New England Journal of Medicine (1946)

IT is the purpose of this paper to discuss the renal reactions that occur after administration of sulfadiazine and to determine whether the clinical criteria generally accepted as indications for discontinuance of the drug are justifiable.The principal toxic reaction to sulfadiazine is renal irritation. Plummer and Wheeler1 reported that of 705 patients receiving 2 to 4 gm. initially, followed by 1 gm. every four hours for not less than two and not more than fourteen days, 8 per cent showed definite evidence of toxicity to sulfadiazine, and that 4.8 per cent had renal irritation. Thus, more than half the . . .
Abstract LB-26: A mathematical methodology for determining the temporal order of pathway alterations in cancer
Authors: Yu-Kang Cheng, Rameen Beroukhim, Ross L. Levine, Ingo K. Mellinghoff, Eric C. Holland, Franziska Michor
Journal: Cancer Research (2011)

Abstract Human cancer is caused by the accumulation of genetic alterations in cells. Of special importance are changes that occur early during malignant transformation because they may result in oncogene addiction and represent promising targets for therapeutic intervention. We have previously described a computational approach, called Retracing the Evolutionary Steps in Cancer (RESIC), to determine the temporal sequence of genetic alterations during tumorigenesis from cross-sectional genomic data of tumors at their fully transformed stage (1). This approach was based on data of alterations in individual genes. Since specific mutational events may not be necessary to cause an oncogenic phenotype and alterations within the set of genes belonging to a particular signaling pathway may have similar or equivalent effects, we apply a pathway-based systems biology approach to the RESIC methodology. This methodology is used to determine whether alterations in specific pathways develop early or late in malignant transformation. When applied to glioblastoma multiforme copy number data from The Cancer Genome Atlas project (2), we find a consistent temporal order of common genetic alterations and the pathways to which the genes belong. These results are also consistent with experimental results that high level EGFR amplification occurs late during gliomagenesis (3–4). This extension to the RESIC methodology provides an evolutionary mathematical approach to identify the temporal sequence of pathway changes driving tumorigenesis and may be useful in guiding the understanding of signaling rearrangements in cancer development. 1. Attolini CS-O, et al. (2010) A mathematical framework to determine the temporal sequence of somatic genetic events in cancer. Proceedings of the National Academy of Sciences 107:17604–17609. 2. TCGA (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455(7216):1061–1068. 3. Bachoo RM, et al. (2002) Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1(3):269–277. 4. Zhu H, et al. (2009) Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis. Proc Natl Acad Sci U S A 106(8):2712–2716. 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 LB-26. doi:10.1158/1538-7445.AM2011-LB-26
ANÁLISIS DE DOS AÑOS DE CPRES EN GIJÓN
Authors: E López, D Pereira, E Barreiro, JM Pérez, MA Álvarez, R García, P Varela, A Mancebo, C De La Coba, M Pipa, FJ Román
Journal: Endoscopy (2014)

Introducción: La Colangio Pancreatografía Retrógrada Endoscópica (CPRE) es clave en el tratamiento/diagnóstico de patologías que afectan a la vía biliar/pancreática. Sin embargo, no está exenta de complicaciones que pueden resultar fatales.
STOP CANCER Reorganizes; New Local Focus
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article STOP CANCER Reorganizes; New Local Focus Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 16, 21 August 1991, Page 1140, https://doi.org/10.1093/jnci/83.16.1140 Published: 21 August 1991
SPONTANEOUSLY-DIFFERENTIATED HUMAN MONOCYTE-DERIVED MACROPHAGES IN PATIENTS WITH CORONARY ARTERY DISEASE: A MORPHO-PHENOTYPIC STUDY
Authors: Nicola Cosentino, Giancarlo Marenzi, Sonia Eligini, Susanna Fiorelli, Franco Fabbiocchi, Marina Camera, Giampaolo Niccoli, Filippo Crea, Elena Tremoli
Journal: Journal of the American College of Cardiology (2016)
Direct peroral pancreatoscopy with an ultraslim endoscope for the evaluation of intraductal papillary mucinous neoplasms
Authors: Y. Cheon, J. Moon, H. Choi, J. Lee, Y. Lee, Y. Cho, T. Lee, S. Park, S. Kim
Journal: Endoscopy (2011)

It is often difficult to distinguish between benign and malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas and to determine their exact extent. Peroral pancreatoscopy including narrow-band imaging (NBI) is useful for the evaluation of these neoplasms [1] [2], but it is technically difficult and requires two skilled endoscopists and endoscopic systems [3]. The ultraslim upper endoscope has been proposed for direct visual examination of the biliopancreatic duct by a single operator [4] [5]. However, the usefulness of direct peroral pancreatoscopy (D-POP) is clinically limited by the inconsistent success rates owing to the inability to keep the position of endoscope stable. An intraductal balloon passed through the endoscope may permit ease of access and stable positioning of the endoscope within the pancreatic duct. After anchoring the intraductal balloon within the proximal pancreatic duct, the endoscope can be advanced over the balloon catheter.
Prevalence of gastrointestinal symptoms after bacterial gastroenteritis
Authors: D. Gorard, P Maxwell, M Mendall, D M Hambidge, R Barber, A Blakey, K R Neal, J Hebden, R C Spiller
Journal: BMJ (1997)

Rationing health careAllocating resources only to treating present dangers would ruin preventive health care and jeopardise future livesEditor-In his article on the objectives of the NHS John Harris argues that "there is a good principle that real and present dangers should be met before future and speculative ones." 1 Has he really thought about the implications of this?Immunisation, health promotion, and preventive interventions would all be swept away in favour of curative treatments.As the lives lost by such a shift in resources would be future lives and the people not identifiable beforehand, they would count for nothing.The state's obligation to protect the "citizen against threats to her life and liberty" only applies to immediate threats.Harris argues that the health budget should be larger, as if a larger budget will somehow allocate itself and obviate the need for choosing between competing alternatives.He also claims that health care (and he means curative care) should be afforded a high priority in the state budget.This presents a simple dilemma: should the state spend more on raising the income of impoverished families or on resources to provide more intensive care beds?Since raising the income of poor families has no impact on immediate threats to health, according to Harris we must clearly prefer spending more on providing more intensive care beds.Harris fails to recognise the first problem in identifying healthcare needs.If resources are not the immediate constraint on a healthcare system then rationing takes place on the basis of whether a need (or a want) can be legitimised as a healthcare need.In times of plenty the remit of formal health care expands.Harris seems to desire this process to continue.In wishing for more of our labour to be devoted to financing this end, he can see no cost or opportunity cost to the process.Am I alone in finding this naive?
AB0451 Changes in DAS28, CDAI and SDAI are Associated with Biologic Class, Gender, Previous Biologic Therapy and ACPA/RF Status – Results from Reuma.PT
Authors: V. Romao, M. Santos, J. Polido-Pereira, C. Duarte, P. Nero, C. Miguel, J. Costa, F. Pimentel-Santos, F. Barcelos, L. Costa, J. Melo Gomes, J. Pereira da Silva, J. Branco, J. Canas da Silva, J. Da Silva, J. Fonseca, H. Canhao
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tocilizumab (TCZ) and anti-tumor necrosis factor (TNF) biologic agents are key therapies in the management of rheumatoid arthritis (RA). They are considered to be equally effective and very few head-to-head comparisons have been published. <h3>Objectives</h3> To compare response to therapy in RA patients treated with anti-TNF agents and TCZ according to different response measures and determine the factors influencing it. <h3>Methods</h3> We included RA patients registered in the Rheumatic Diseases Portuguese Register, Reuma.pt, who started anti-TNF or TCZ after January 1, 2008, were treated for at least 6 months and had available DAS28 scores at baseline and at 6 months. Our primary outcome was the change in DAS28, CDAI and SDAI at 6 months. We performed linear regressions to compare the groups and determined the best model predicting change in disease activity for each index. <h3>Results</h3> 524 RA patients were enrolled, (106 adalimumab, 202 etanercept, 43 golimumab, 78 infliximab, 95 TCZ). At baseline, TCZ users were less frequently naïve to biologic therapies (54.7% vs. 85%, p&lt;0.0001), had more swollen and tender joint counts (p&lt;0.0001 and p=0.02, respectively) and higher disease activity according to all indexes: DAS28 6.1±1.1 vs. 5.4±1.3 (n=524, p&lt;0.0001), CDAI 33.3±13.2 vs. 28.1±13.6 (n=376, p=0.005), SDAI.35.6±13.1 vs. 29.1±30.4 (n=361, p=0.004). At 6 months, change in DAS28, CDAI, SDAI and joint counts was significantly higher in the TCZ group (Table 1). Multivariate linear regression models best predicting change in disease activity included biologic class, number of previous biologics, baseline activity, gender and ACPA/RF status (Table 2). Compared to anti-TNF, TCZ was associated with a larger difference in ΔDAS28, ΔCDAI and ΔSDAI of, respectively, 1.45, 4.25 and 5.41. <h3>Conclusions</h3> TCZ treatment was associated with greater change in DAS28, CDAI, SDAI and joint counts at 6 months. Biologic class, number of previous biologics, baseline activity, gender and ACPA/RF status predicted change in disease activity. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3414
O100 DISCOVERY OF NOVEL MUTATIONS AND FUSION PROTEINS IN INTRAHEPATIC CHOLANGIOCARCINOMA
Authors: D. Sia, B. Losic, L. Cabellos, A. Moeini, K. Revill, D. Bonal, K. Hao, O. Miltiadous, Z. Zhang, Y. Hoshida, M. Castillo, S. Roayaie, S. Thung, M. Schwartz, S. Waxman, C. Cordon-Cardo, V. Mazzaferro, E. Schadt, J.M. Llovet
Journal: Journal of Hepatology (2014)
AB0719 2-Year Incidence of New Immune-Mediated Inflamatory Diseases in Patients with Spondyloarthritis. the Aquiles Study
Authors: R. García-Vicuna, P. Zarco, C.M. Gonzalez, A. Rodríguez de la Serna, E. Peiro, I. Mateo, L. Linares, J. Calvo, S. Fernandez, L. Cea-Calvo, M.J. Arteaga, I. Marín-Jiménez, F. Vanaclocha
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Patients with spondyloarthritis (SpA) frequently show other immune-mediated inflammatory diseases (IMID) <h3>Objectives</h3> To describe the 2-year incidence of new diagnoses of IMID in patients with SpA recruited for the AQUILES study <h3>Methods</h3> AQUILES was a prospective observational study on 3 independent cohorts of patients aged ≥18 years-old with SpA, inflammatory bowel disease (IBD) or psoriasis recruited from rheumatology, IBD and dermatology offices from 15 hospitals in Spain. Patients were followed for 2 years. In the SpA cohort, the diagnosis of new IMID was based on reports from gastroenterologists (IBD), dermatologists (psoriasis) or ophthalmologists (uveitis) <h3>Results</h3> A total of 513 patients with SpA completed the 2-year follow-up (mean age: 48 years-old; 37.5% females, 62.5% males). Median duration of disease was 7.8 years. The diagnoses at baseline were: ankylosing spondylitis (AS) (n=285), psoriatic arthritis (PsA) (n=130), enteropathic arthritis (n=13), undifferentiated arthritis (n=83) and others (n=2). At baseline, 45% had other IMID (4.9% IBD; 28.7% psoriasis; 14.6% uveitis). During the 2-year period, 22 new diagnoses of incident IMID were recorded (cumulative incidence: 4.3%, 95% CI: 2.4-6.1; incidence rate: 17 cases per 10,000 patients-year). The predominant incident IMID was uveitis (16 cases, cumulative incidence 3.1%, 95% CI: 1.5-4.7). In the subgroup with AS, there were 16 new cases of IMID (5.6%; 13 of them uveitis [4.6%], 1 IBD [0.4%] and 2 psoriasis [0.8%]). In patients with PsA only 2 patients developed a new IMID (2 new diagnoses of psoriasis [1.5%]). In those with undifferentiated SpA, there were 2 new diagnoses of uveitis (2.4%) and 1 psoriasis (1.2%), and 1 patient with enteropathic arthritis developed uveitis. There were no differences in the incidence by patient9s age, gender, duration of disease, extra-articular manifestations or family history of SpA, and the multivariate analysis identified the diagnosis of AS as the only predictor of development of new IMID (OR: 3.5 [1.0-15.3, p=0.049] versus psoriatic arthritis) <h3>Conclusions</h3> In SpA patients recruited for the AQUILES study, the 2-year cumulative incidence of new IMID was 4.3%, mostly due to new patients with diagnosis of uveitis in patients with AS. Diagnosis of AS at baseline was the only predictor for the development of a new IMID <h3>Acknowledgements</h3> The AQUILES study was funded by Merck Sharp &amp; Dohme of Spain. The authors thank the investigators for the recruitment and follow-up of patients <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3090