tbuckley/cabot-search huggingface dataset:
Abstract 1036: Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition
Authors: Daisuke Matsubara, Reem Ibrahim, Wael Osman, Akteru Goto, Teppei Morikawa, Shigeki Morita, Shumpei Ishikawa, Hiroyuki Aburatani, Masashi Fukayama, Toshiro Niki, Yoshinori Murakami
Journal: Cancer Research (2014)

Abstract Although protein arginine methyltransferase 5 (PRMT5) has been implicated in various cancers, its expression pattern in lung adenocarcinoma cell lines and tissue samples has not yet been elucidated in detail. In this study, microarray data analysis of 40 non-small cell lung carcinoma cell lines showed that PRMT5 was a candidate histone methyltransferase gene that correlated with epithelial-mesenchymal transition. Immunocytochemical analysis of these cell lines indicated that the expression of PRMT5 was frequently localized to the cytoplasm of E-cadherin-low and vimentin-high cell lines, while it was predominant in the nucleus and faint in the cytoplasm of E-cadherin-high and vimentin-low cell lines. Immunohistochemical analysis of 130 cases of lung adenocarcinoma revealed that the expression of PRMT5 was high in the cytoplasm of 47 cases (36%) and the nuclei of 34 cases (26%). The high cytoplasmic expression of PRMT5 was frequently observed in high grade subtypes such as the solid adenocarcinoma component with low expression of thyroid transcription factor-1 (TTF-1, the master regulator of lung) and low expression of cytokeratin 7 and E-cadherin (two markers for bronchial epithelial differentiation), while the high nuclear expression of PRMT5 was frequently noted in the lepidic growth component, a low-grade subtype. The cytoplasmic expression of PRMT5 was correlated with vessel invasion and poor prognosis. We herein highlighted the importance of PRMT5 expression, especially its cytoplasmic expression, in the process of epithelial-mesenchymal transition and loss of the bronchial epithelial phenotype of lung adenocarcinoma. Citation Format: Daisuke Matsubara, Reem Ibrahim, Wael Osman, Akteru Goto, Teppei Morikawa, Shigeki Morita, Shumpei Ishikawa, Hiroyuki Aburatani, Masashi Fukayama, Toshiro Niki, Yoshinori Murakami. Expression of PRMT5 in lung adenocarcinoma and its significance in epithelial-mesenchymal transition. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1036. doi:10.1158/1538-7445.AM2014-1036
Randomized, Placebo-Controlled, Phase II Study of Sequential Erlotinib and Chemotherapy As First-Line Treatment for Advanced Non–Small-Cell Lung Cancer
Authors: Tony S.K. Mok, Yi-Long Wu, Chong-Jen Yu, Caicun Zhou, Yuh-Min Chen, Li Zhang, Jorge Ignacio, Meilin Liao, Vichien Srimuninnimit, Michael J. Boyer, Marina Chua-Tan, Virote Sriuranpong, Aru W. Sudoyo, Kate Jin, Michael Johnston, Winsome Chui, Jin-Soo Lee
Journal: Journal of Clinical Oncology (2009)

This study investigated whether sequential administration of erlotinib and chemotherapy improves clinical outcomes versus chemotherapy alone in unselected, chemotherapy-naïve patients with advanced non-small-cell lung cancer (NSCLC).Previously untreated patients (n = 154) with stage IIIB or IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned to receive erlotinib (150 mg/d) or placebo on days 15 to 28 of a 4-week cycle that included gemcitabine (1,250 mg/m(2) days 1 and 8) and either cisplatin (75 mg/m(2) day 1) or carboplatin (5 x area under the serum concentration-time curve, day 1). The primary end point was nonprogression rate (NPR) at 8 weeks. Secondary end points included tumor response rate, NPR at 16 weeks, duration of response, progression-free survival (PFS), overall survival (OS), and safety.The NPR at 8 weeks was 80.3% in the gemcitabine plus cisplatin or carboplatin (GC)-erlotinib arm (n = 76) and 76.9% in the GC-placebo arm (n = 78). At 16 weeks, the NPR was 64.5% for GC-erlotinib versus 53.8% for GC-placebo. The response rate was 35.5% for GC-erlotinib versus 24.4% for GC-placebo. PFS was significantly longer with GC-erlotinib than with GC-placebo (adjusted hazard ratio, 0.47; log-rank P = .0002; median, 29.4 v 23.4 weeks); this benefit was consistent across all clinical subgroups. There was no significant difference in OS. The addition of erlotinib to chemotherapy was well tolerated, with no increase in hematologic toxicity, and no treatment-related interstitial lung disease.Sequential administration of erlotinib following gemcitabine/platinum chemotherapy led to a significant improvement in PFS. This treatment approach warrants further investigation in a phase III study.
Economic Analysis of the TAX 317 Trial: Docetaxel Versus Best Supportive Care as Second-Line Therapy of Advanced Non-Small-Cell Lung Cancer
Authors: Natasha B. Leighl, Frances A. Shepherd, Rita Kwong, Ronald L. Burkes, Ronald Feld, Pamela J. Goodwin
Journal: Journal of Clinical Oncology (2002)

PURPOSE: To determine the cost-effectiveness (CE) of second-line docetaxel compared with best supportive care (BSC) in the TAX 317 trial, a randomized clinical trial of second-line chemotherapy in non–small-cell lung cancer. METHODS: A retrospective CE analysis of the TAX 317 trial was undertaken, evaluating direct medical costs of therapy from the viewpoint of Canada’s public health care system. Costs were derived in 1999 Canadian dollars, and resource use was determined through prospective trial data. RESULTS: The incremental survival benefit in the docetaxel arm over BSC was 2 months (P = .047). The CE of docetaxel was $57,749 per year of life gained. For patients treated with docetaxel 75 mg/m2, the CE was $31,776 per year of life gained. In univariate sensitivity analyses, CE estimates were most sensitive to changes in survival, ranging from $18,374 to $117,434 with 20% variation in survival at the recommended dose. The largest cost center in both arms was hospitalization, followed by the cost of dru...
Proteasome Enzymatic Activities in Plasma as Risk Stratification of Patients with Acute Myeloid Leukemia and Advanced-Stage Myelodysplastic Syndrome
Authors: Wanlong Ma, Hagop Kantarjian, Benjamin Bekele, Amber C. Donahue, Xi Zhang, Zhong J. Zhang, Susan O'Brien, Elihu Estey, Zeev Estrov, Jorge Cortes, Michael Keating, Francis Giles, Maher Albitar
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Cytogenetic abnormalities are currently the most important predictors of response and clinical outcome for patients with acute myeloid leukemia (AML) or advanced-stage myelodysplastic syndrome (MDS). Because clinical outcomes vary markedly within cytogenetic subgroups, additional biological markers are needed for risk stratification. Experimental Design: We assessed the utility of measuring pretreatment proteasome chymotrypsin-like, caspase-like, and trypsin-like activities in plasma to predict response and survival of patients with AML (n = 174) or advanced-stage MDS (n = 52). Results: All three enzymatic activities were significantly (P &amp;lt; 0.001) increased in the plasma of patients with AML and MDS compared with normal controls. Both chymotrypsin-like and caspase-like activities, but not trypsin-like activity, correlated with outcome. Chymotrypsin-like and caspase-like activities, but not trypsin-like activity, predicted response in univariate analysis (P = 0.002). However, only chymotrypsin-like activity was independent predictor of response from age grouping (&amp;lt;70 versus ≥70 years), cytogenetics, and blood urea nitrogen in multivariate analysis. Similarly, both chymotrypsin-like and caspase-like activities, but not trypsin-like activity, were predictors of overall survival in univariate analysis (P &amp;lt; 0.0001), but only chymotrypsin-like activity was independent of cytogenetics, age, performance status, blood urea nitrogen, and β2-microglobulin in multivariate Cox regression models. Chymotrypsin-like activity was also a strong independent predictor of survival in patients with intermediate karyotype (n = 124). Conclusions: Measuring plasma chymotrypsin-like activity may provide a powerful biomarker for risk stratification in patients with AML and advanced-stage MDS, including those with normal karyotype.
Divergent Pro- and Antiinflammatory Roles for IL-23 and IL-12 in Joint Autoimmune Inflammation
Authors: Craig A. Murphy, Claire L. Langrish, Yi Chen, Wendy Blumenschein, Terrill McClanahan, Robert A. Kastelein, Jonathon D. Sedgwick, Daniel J. Cua
Journal: The Journal of Experimental Medicine (2003)

Interleukin (IL) 23 is a heterodimeric cytokine composed of a p19 subunit and the p40 subunit of IL-12. IL-23 affects memory T cell and inflammatory macrophage function through engagement of a novel receptor (IL-23R) on these cells. Recent analysis of the contribution of IL-12 and IL-23 to central nervous system autoimmune inflammation demonstrated that IL-23 rather than IL-12 was the essential cytokine. Using gene-targeted mice lacking only IL-12 (p35−/−) or IL-23 (p19−/−), we show that the specific absence of IL-23 is protective, whereas loss of IL-12 exacerbates collagen-induced arthritis. IL-23 gene-targeted mice did not develop clinical signs of disease and were completely resistant to the development of joint and bone pathology. Resistance correlated with an absence of IL-17–producing CD4+ T cells despite normal induction of collagen-specific, interferon-γ–producing T helper 1 cells. In contrast, IL-12–deficient p35−/− mice developed more IL-17–producing CD4+ T cells, as well as elevated mRNA expression of proinflammatory tumor necrosis factor, IL-1β, IL-6, and IL-17 in affected tissues of diseased mice. The data presented here indicate that IL-23 is an essential promoter of end-stage joint autoimmune inflammation, whereas IL-12 paradoxically mediates protection from autoimmune inflammation.
Quantitative Assay for Lectin-Induced Cytoagglutination by Means of an Electronic Particle-Counting Technique 234
Authors: G.P. Phondke, K.R. Madyastha, Rolf F. Barth
Journal: JNCI Journal of the National Cancer Institute (1981)

Quantitative Assay for Lectin-Induced Cytoagglutination by Means of an Electronic Particle-Counting Technique Get access G.P. Phondke, G.P. Phondke 5Bio-Medical Group, Bhabha Atomic Research Center, Trombay 400085, India. Search for other works by this author on: Oxford Academic PubMed Google Scholar K.R. Madyastha, K.R. Madyastha 6Department of Basic and Clinical Immunology, Medical University of South Carolina, Charleston, S.C. 29403. Search for other works by this author on: Oxford Academic PubMed Google Scholar Rolf F. Barth Rolf F. Barth 7 7Address reprint requests toDr. Barth at Department of Pathology, The Ohio State University, 333 West 10th Ave., Columbus, Ohio 43210. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 4, April 1981, Pages 637–642, https://doi.org/10.1093/jnci/66.4.637 Published: 01 April 1981 Article history Received: 17 June 1946 Accepted: 29 October 1946 Published: 01 April 1981
Antineutrophil Cytoplasmic Autoantibody–Negative Pauci-immune Crescentic Glomerulonephritis
Authors: Min Chen, Feng Yu, Su-Xia Wang, Wan-Zhong Zou, Ming-Hui Zhao, Hai-Yan Wang
Journal: Journal of the American Society of Nephrology (2007)

Pauci-immune crescentic glomerulonephritis (CrGN) is one of the most common causes of rapidly progressive glomerulonephritis. The majority of patients with pauci-immune CrGN had circulating antineutrophil cytoplasmic autoantibody (ANCA). However, patients with ANCA-negative pauci-immune CrGN were not investigated fully. This study aimed to analyze the characteristics of this subgroup of patients. Patients whose pauci-immune CrGN was diagnosed from 1997 to 2006 in one center were studied retrospectively. The criteria of pauci-immune was defined as "the intensity of glomerular immunoglobulins staining by direct immunofluorescence assay in renal sections was negative to 1+ staining on a scale of 0 to 4+." Clinical and pathologic characteristics were compared between patients with and without ANCA. Among the 85 patients with pauci-immune CrGN, 28 (32.9%) were ANCA negative. Compared with the 57 ANCA-positive patients, the ANCA-negative patients were much younger (39.7 +/- 17.0 versus 57.6 +/- 14.0 yr; P < 0.001). The level of urinary protein and the prevalence of nephrotic syndrome were significantly higher in ANCA-negative patients than that in ANCA-positive patients (P < 0.01 and P < 0.001, respectively). However, the prevalence of extrarenal involvement was significantly lower in ANCA-negative patients than that in ANCA-positive patients. The renal survival was poorer in ANCA-negative patients than that in ANCA-positive ones (P < 0.05). ANCA-negative pauci-immune CrGN was not rare and might represent an independent disease entity from ANCA-positive vasculitis.
Steroid administration after myocardial infarction promotes early infarct expansion. A study in the rat.
Authors: J A Mannisi, H F Weisman, D E Bush, P Dudeck, B Healy
Journal: Journal of Clinical Investigation (1987)

Whether steroids lead to thinner scars and larger aneurysms by delaying collagen deposition or worsening infarct expansion before significant collagen deposition begins is unknown. Rats underwent either transmural infarction by left coronary ligation or sham operation. Both infarct and sham rats were randomized to methylprednisolone 50 mg/kg i.p. X 4 or saline treatment within 24 h after operation. Sacrifice occurred before (3 d) or after (7 d) collagen deposition typically begins. Despite similar infarct size, infarct wall thickness was 1.35 +/- 0.08 mm in the saline and 0.99 +/- 0.12 mm in the methylprednisolone group (P less than 0.001) at 3 d. This decrease in wall thickness was explained by a decrease in the number of myocytes across the infarct wall (r = 0.99; P less than 0.001), suggesting that steroids promote myocyte slippage. Furthermore, methylprednisolone caused no further infarct thinning or cavity dilatation beyond 3 d. Thus, high-dose methylprednisolone given within 24 h after transmural infarction worsens infarct expansion before collagen is laid down by promoting the slippage of necrotic myocytes.
Bariatric surgery as urate-lowering therapy in severe obesity
Authors: Hyon K Choi, Yuqing Zhang
Journal: Annals of the Rheumatic Diseases (2014)

Gout represents a metabolically driven inflammatory arthropathy, which could be substantially influenced by adiposity and lifestyle risk factors. As such, influenced by the trends in lifestyle factors associated with Westernisation,1 ,2 gout prevalence has increased in the last few decades worldwide (eg, 3.9% of US adults (8.3 million) in 2007–20083).4 The disease burden of gout has been further complicated by a high level of cardiovascular (CV)–metabolic comorbidities (eg, hypertension in 74%; obesity in 53%5) and their sequelae (eg, increased future risk of myocardial infarction and premature death6 ,7).

Among many known modifiable risk factors for hyperuricaemia and gout, obesity is one of the strongest, as observed in many prospective cohort studies.8–12 To date, few medical interventions, except bariatric surgery, have been effective in the treatment of obesity. Indeed, studies have shown that bariatric surgery not only induces substantial weight loss but also greatly improves key obesity-related CV–metabolic abnormalities and outcomes,13–15 including blood pressure, glucose, insulin, triglycerides, high-density lipoprotein (HDL)-cholesterol, serum uric acid (SUA) levels16 and overall mortality.17

In their timely study, Dalbeth et al 18 sought to examine the potential pathogenetic and clinical relevance of the urate-lowering benefits of bariatric surgery. Over 1 year of prospective follow-up of 60 individuals with severe obesity (body mass index (BMI) ≥35 kg/m2) and type 2 diabetes, bariatric surgery led to a weight reduction of 34 kg, and proportions of those with SUA levels higher than the urate saturation point and the usual urate-lowering therapy (ULT) target (SUA=0.36 mmol/L)19 declined by 37% and 41%, respectively. Among the 12 gout patients included in this study, the proportion of SUA above 0.36 mmol/L declined from 83% (10/12) at baseline to 33% (4/12) 1 year after surgery; the corresponding proportion of ULT use also declined from 75% (9/12) …
Molecular Imaging of Apoptosis: From Micro to Macro
Authors: Wenbin Zeng, Xiaobo Wang, Pengfei Xu, Gang Liu, Henry S. Eden, Xiaoyuan Chen
Journal: Theranostics (2015)

Apoptosis, or programmed cell death, is involved in numerous human conditions including neurodegenerative diseases, ischemic damage, autoimmune disorders and many types of cancer, and is often confused with other types of cell death.Therefore strategies that enable visualized detection of apoptosis would be of enormous benefit in the clinic for diagnosis, patient management, and development of new therapies.In recent years, improved understanding of the apoptotic machinery and progress in imaging modalities have provided opportunities for researchers to formulate microscopic and macroscopic imaging strategies based on well-defined molecular markers and/or physiological features.Correspondingly, a large collection of apoptosis imaging probes and approaches have been documented in preclinical and clinical studies.In this review, we mainly discuss microscopic imaging assays and macroscopic imaging probes, ranging in complexity from simple attachments of reporter moieties to proteins that interact with apoptotic biomarkers, to rationally designed probes that target biochemical changes.Their clinical translation will also be our focus.
Aerosolized iloprost induces a mild but sustained inhibition of platelet aggregation
Authors: M. Beghetti, G. Reber, P. de Moerloose, L. Vadas, A. Chiappe, I. Spahr-Schopfer, P.C. Rimensberger
Journal: European Respiratory Journal (2002)

Pathological studies have revealed that one of the main features encountered in the pulmonary vasculature of patients with pulmonary hypertension is the presence of thrombotic lesions. Open pilot studies have indicated that aerosolized iloprost may have beneficial effects in patients with pulmonary hypertension. The effects of aerosolized iloprost on platelet function and plasma cyclic adenosine monophosphate (cAMP) were studied. Platelet aggregation and plasma cAMP were measured at baseline, 30 min, 4 and 6 h after inhalation of 15 µg iloprost in 10 healthy volunteers. Maximal platelet aggregation in response to adenosine diphosphate (ADP) (2 and 6 µmol·L<sup>−1</sup>), collagen (2.5 and 5 µg·mL<sup>−1</sup>), epinephrine (1.25 and 5 µmol·L<sup>−1</sup>) and arachidonic acid (0.5 mg·mL<sup>−1</sup>) was measured. Platelet aggregation was significantly inhibited at 30 min in response to ADP (2 and 6 µmol·L<sup>−1</sup>, epinephrine (1.25 and 5 µmol·L<sup>−1</sup>) and collagen (2.5 µg·mL<sup>−1</sup>). It was still inhibited at 4 h in response to the same agents, but normalized at 6 h. cAMP increased at 30 min, from 27.3±1.2 to 31.8±1.2 nmol·L<sup>−1</sup>, remained increased at 4 h (29.2±1.3 nmol·L<sup>−1</sup>) and normalized at 6 h (27.4±1.1 nmol·L<sup>−1</sup>). Aerosolized iloprost induced a mild but sustained inhibition of platelet aggregation. Platelet aggregation inhibition may be one of the mechanisms which explains the beneficial effect of repeated inhalation of iloprost in pulmonary hypertension.
Prevalence of asthma among schoolchildren in Patras, Greece: three surveys over 20 years
Authors: M Anthracopoulos, A Karatza, E Liolios, M Triga, K Triantou, K Priftis
Journal: Thorax (2001)

The aim of the present study was to compare the prevalence of asthma among schoolchildren in 1978, 1991, and 1998 in Patras, Greece.The study populations of the three comparable cross sectional surveys comprised third and fourth grade public school children in Patras, Greece. Sample sizes in 1978, 1991, and 1998 were 3735, 2952 and 3397 children and response rates were 80.4%, 81.9%, and 90.6%, respectively. Prevalence of current, non-current, and lifetime asthma or recurrent wheezing was determined by parental questionnaire. Personal communication with the parents of asthmatic children in 1991 and 1998 provided data on lost schooldays.Prevalence rates of current asthma or wheezing in 1978, 1991, and 1998 were 1.5%, 4.6%, and 6.0%, respectively (1978-91: p=0.01, 1991-98: p=0.02, 1978-98: p=0.03). Lifetime prevalences of asthma or wheezing in 1991 and 1998 were 8.0% and 9.6%, respectively (p=0.03). Current diagnosed asthma increased proportionally to diagnosed wheezing during 1991-98. The number of schooldays lost in the previous 2 years because of asthma did not change (p>0.1) between 1991 (0.31 per child) and 1998 (0.34 per child).Our results support a true increase in the prevalence of current and lifetime asthma in the last 20 years among pre-adolescent children in Patras, Greece.
A New Rodent Model to Assess Blood Stage Immunity to the <i>Plasmodium falciparum</i> Antigen Merozoite Surface Protein 119 Reveals a Protective Role for Invasion Inhibitory Antibodies
Authors: Tania F. de Koning-Ward, Rebecca A. O'Donnell, Damien R. Drew, Russell Thomson, Terence P. Speed, Brendan S. Crabb
Journal: The Journal of Experimental Medicine (2003)

Antibodies capable of inhibiting the invasion of Plasmodium merozoites into erythrocytes are present in individuals that are clinically immune to the malaria parasite. Those targeting the 19-kD COOH-terminal domain of the major merozoite surface protein (MSP)-119 are a major component of this inhibitory activity. However, it has been difficult to assess the overall relevance of such antibodies to antiparasite immunity. Here we use an allelic replacement approach to generate a rodent malaria parasite (Plasmodium berghei) that expresses a human malaria (Plasmodium falciparum) form of MSP-119. We show that mice made semi-immune to this parasite line generate high levels of merozoite inhibitory antibodies that are specific for P. falciparum MSP-119. Importantly, protection from homologous blood stage challenge in these mice correlated with levels of P. falciparum MSP-119-specific inhibitory antibodies, but not with titres of total MSP-119-specific immunoglobulins. We conclude that merozoite inhibitory antibodies generated in response to infection can play a significant role in suppressing parasitemia in vivo. This study provides a strong impetus for the development of blood stage vaccines designed to generate invasion inhibitory antibodies and offers a new animal model to trial P. falciparum MSP-119 vaccines.