tbuckley/cabot-search huggingface dataset:
Mesothelin Overexpression Promotes Mesothelioma Cell Invasion and MMP-9 Secretion in an Orthotopic Mouse Model and in Epithelioid Pleural Mesothelioma Patients
Authors: Elliot L. Servais, Christos Colovos, Luis Rodriguez, Adam J. Bograd, Jun-ichi Nitadori, Camelia Sima, Valerie W. Rusch, Michel Sadelain, Prasad S. Adusumilli
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Mesothelin (MSLN) is a tumor-associated antigen, being investigated as a biomarker and therapeutic target in malignant pleural mesothelioma (MPM). The biologic function of MSLN overexpression in MPM is unknown. We hypothesized that MSLN may promote tumor invasion in MPM, a tumor characterized primarily by regional aggressiveness and rare distant metastases. Experimental Design: Human and murine MPM cells with MSLN forced expression and short hairpin RNA knockdown were examined for proliferation, invasion, and matrix metalloproteinase (MMP) secretion. The influence of MSLN overexpression on MPM cell invasion was assessed in an orthotopic mouse model and in patient samples. Results: MSLN expression promotes MPM cell invasion and MMP secretion in both human and murine MPM cells. In an orthotopic MPM mouse model characterized by our laboratory, MPM cells with MSLN overexpression preferentially localized to the tumor invading edge, colocalized with MMP-9 expression, and promoted decreased survival without an increase in tumor burden progression. In a tissue microarray from epithelioid MPM patients (n = 139, 729 cores), MSLN overexpression correlated with higher MMP-9 expression at individual core level. Among stage III MPM patients (n = 72), high MSLN expression was observed in 26% of T2 tumors and 51% of T3 tumors. Conclusions: Our data provide evidence elucidating a biologic role for MSLN as a factor promoting tumor invasion and MMP-9 expression in MSLN expressing MPM. As regional invasion is the characteristic feature in MSLN expressing solid cancers (MPM, pancreas, and ovarian), our observations add rationale to studies investigating MSLN as a therapeutic target. Clin Cancer Res; 18(9); 2478–89. ©2012 AACR.
Gap Junctions in Cardiovascular Disease
Authors: Habo J. Jongsma, Ronald Wilders
Journal: Circulation Research (2000)

Abstract —Connexins, the protein molecules forming gap junction channels, are reduced in number or redistributed from intercalated disks to lateral cell borders in a variety of cardiac diseases. This “gap junction remodeling” is considered to be arrhythmogenic. Using a simple model of human ventricular myocardium, we found that quantitative remodeling data extracted from the literature gave rise to only small to moderate changes in conduction velocity and the anisotropy ratio. Especially for longitudinal conduction, cytoplasmic resistivity (and thus cellular geometry) is much more important than commonly realized. None of the remodeling data gave rise to slow conduction on the order of a few centimeters per second.
Whither whole brain radiotherapy for primary CNS lymphoma?
Authors: L. M. DeAngelis
Journal: Neuro-Oncology (2014)

Primary central nervous system lymphoma (PCNSL) is a relatively rare form of extra-nodal non-Hodgkin's lymphoma that accounts for approximately 4% of primary central nervous system tumors.Treatment with high-dose methotrexate-based chemotherapeutic regimens have resulted in response rates of 60-70% or higher and long-term survival in 15-30% of patients. 1 -4 While PCNSL is sensitive to radiation therapy, the duration of response is relatively short, and treatment is associated with delayed neurotoxicity, especially in the elderly. 5 Increasingly, there is a debate regarding the value of radiation therapy in the initial treatment of patients with PCNSL.This is reflected in the two ongoing randomized studies of newly diagnosed PCNSL being conducted in the United States.One, sponsored by NRG Oncology, evaluates the value of adding radiation therapy to chemotherapy (NCT01399372).In contrast, a second study, conducted by the Alliance in Clinical Trials in Oncology Cooperative Group, eliminates radiation therapy completely and compares standard chemotherapy alone with chemotherapy followed by autologous stem cell transplantation (NCT01511562).In the subsequent articles, Dr.
Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer
Authors: Cunxi Li, Haiting Ma, Yang Wang, Zheng Cao, Ramona Graves-Deal, Anne E. Powell, Alina Starchenko, Gregory D. Ayers, Mary Kay Washington, Vidya Kamath, Keyur Desai, Michael J. Gerdes, Lila Solnica-Krezel, Robert J. Coffey
Journal: Journal of Clinical Investigation (2014)

The epithelial-to-mesenchymal transition (EMT) transcriptional program is characterized by repression of E-cadherin (CDH1) and induction of N-cadherin (CDH2), and mesenchymal genes like vimentin (VIM). Placenta-specific 8 (PLAC8) has been implicated in colon cancer; however, how PLAC8 contributes to disease is unknown, and endogenous PLAC8 protein has not been studied. We analyzed zebrafish and human tissues and found that endogenous PLAC8 localizes to the apical domain of differentiated intestinal epithelium. Colon cancer cells with elevated PLAC8 levels exhibited EMT features, including increased expression of VIM and zinc finger E-box binding homeobox 1 (ZEB1), aberrant cell motility, and increased invasiveness. In contrast to classical EMT, PLAC8 overexpression reduced cell surface CDH1 and upregulated P-cadherin (CDH3) without affecting CDH2 expression. PLAC8-induced EMT was linked to increased phosphorylated ERK2 (p-ERK2), and ERK2 knockdown restored cell surface CDH1 and suppressed CDH3, VIM, and ZEB1 upregulation. In vitro, PLAC8 directly bound and inactivated the ERK2 phosphatase DUSP6, thereby increasing p-ERK2. In a murine xenograft model, knockdown of endogenous PLAC8 in colon cancer cells resulted in smaller tumors, reduced local invasion, and decreased p-ERK2. Using MultiOmyx, a multiplex immunofluorescence-based methodology, we observed coexpression of cytosolic PLAC8, CDH3, and VIM at the leading edge of a human colorectal tumor, supporting a role for PLAC8 in cancer invasion in vivo.
Intravascular histiocytosis associated with rheumatoid arthritis: report of a case with lymphatic endothelial proliferation
Authors: A. Okazaki, H. Asada, H. Niizeki, A. Nonomura, S. Miyagawa
Journal: British Journal of Dermatology (2005)

Journal Article Intravascular histiocytosis associated with rheumatoid arthritis: report of a case with lymphatic endothelial proliferation Get access A. Okazaki, A. Okazaki Departments of Dermatology and *Clinical Pathology, Nara Medical University School of Medicine, Kashihara City, Nara 634‐8522, Japan E‐mail: sachikom@naramed‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar H. Asada, H. Asada Departments of Dermatology and *Clinical Pathology, Nara Medical University School of Medicine, Kashihara City, Nara 634‐8522, Japan E‐mail: sachikom@naramed‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar H. Niizeki, H. Niizeki Departments of Dermatology and *Clinical Pathology, Nara Medical University School of Medicine, Kashihara City, Nara 634‐8522, Japan E‐mail: sachikom@naramed‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar A. Nonomura, A. Nonomura Departments of Dermatology and *Clinical Pathology, Nara Medical University School of Medicine, Kashihara City, Nara 634‐8522, Japan E‐mail: sachikom@naramed‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar S. Miyagawa S. Miyagawa Departments of Dermatology and *Clinical Pathology, Nara Medical University School of Medicine, Kashihara City, Nara 634‐8522, Japan E‐mail: sachikom@naramed‐u.ac.jp Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 6, 1 June 2005, Pages 1385–1387, https://doi.org/10.1111/j.1365-2133.2005.06618.x Published: 01 June 2005
Guidelines International Network: Principles for Disclosure of Interests and Management of Conflicts in Guidelines
Authors: Holger J. Schünemann, Lubna A. Al-Ansary, Frode Forland, Sonja Kersten, Jorma Komulainen, Ina B. Kopp, Fergus Macbeth, Susan M. Phillips, Craig Robbins, Philip van der Wees, Amir Qaseem
Journal: Annals of Internal Medicine (2015)

Conflicts of interest (COIs) have been defined by the American Thoracic Society as "a divergence between an individual's private interests and his or her professional obligations such that an independent observer might reasonably question whether the individual's professional actions or decisions are motivated by personal gain, such as direct financial, academic advancement, clinical revenue streams, or community standing." In the context of guideline development, the concerns are not simply about identifying and disclosing direct financial or indirect COIs. Despite this recognition, the management of COIs in guidelines is often unsatisfactory. In response to requests from its international membership and informed by existing syntheses of the evidence and policies of international organizations, the Guidelines International Network Board of Trustees developed guidance on the disclosure of interests and management of COIs. Current approaches are relatively similar throughout the guideline development community, with an increasing recognition of the importance of disclosing and managing indirect COIs. Although there are differences in detail among the approaches, the similarities allow for the formulation of 9 core principles for managing COIs. In formulating these principles, the Guidelines International Network Board of Trustees recognizes that COIs cannot be totally avoided when panel members are being chosen for certain guidelines or in certain settings; thus, the important issue is the management of COIs in a fair, judicious, transparent manner.
Lysozyme synthesis by established human and murine histiocytic lymphoma cell lines.
Authors: P Ralph, M A Moore, K Nilsson
Journal: The Journal of Experimental Medicine (1976)

A human cell line established in culture from a histiocytic lymphoma patient synthesizes and secretes the monocyte-granulocyte specific enzyme lysozyme. 18 other human cell lines with characteristics of T-lymphocyte, B-lymphocyte, Burkitt's lymphoma, non-Burkitt's lymphoma, myeloma, and bone marrow epithelial cells were not associated with lysozyme. Among murine cell lines, lysozyme was produced by (a) three histiocytic lymphoma or macrophage lines, which mediate antibody-dependent phagocytosis and cytolysis; (b) myelomonocytic leukemia line which also secretes myeloid colony-stimulating factor; and (c) a spontaneous lymphoma and an Abelson leukemia virus-induced lymphoma. Lysozyme-negative lines include another Abelson lymphoma, myelomas, T lymphomas, and mastocytoma.
Predicting Cancer Drug Response by Proteomic Profiling
Authors: Yan Ma, Zhenyu Ding, Yong Qian, Xianglin Shi, Vince Castranova, E. James Harner, Lan Guo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Accurate prediction of an individual patient's drug response is an important prerequisite of personalized medicine. Recent pharmacogenomics research in chemosensitivity prediction has studied the gene-drug correlation based on transcriptional profiling. However, proteomic profiling will more directly solve the current functional and pharmacologic problems. We sought to determine whether proteomic signatures of untreated cells were sufficient for the prediction of drug response. Experimental Design: In this study, a machine learning model system was developed to classify cell line chemosensitivity exclusively based on proteomic profiling. Using reverse-phase protein lysate microarrays, protein expression levels were measured by 52 antibodies in a panel of 60 human cancer cell (NCI-60) lines. The model system combined several well-known algorithms, including random forests, Relief, and the nearest neighbor methods, to construct the protein expression–based chemosensitivity classifiers. The classifiers were designed to be independent of the tissue origin of the cells. Results: A total of 118 classifiers of the complete range of drug responses (sensitive, intermediate, and resistant) were generated for the evaluated anticancer drugs, one for each agent. The accuracy of chemosensitivity prediction of all the evaluated 118 agents was significantly higher (P &amp;lt; 0.02) than that of random prediction. Furthermore, our study found that the proteomic determinants for chemosensitivity of 5-fluorouracil were also potential diagnostic markers of colon cancer. Conclusions: The results showed that it was feasible to accurately predict chemosensitivity by proteomic approaches. This study provides a basis for the prediction of drug response based on protein markers in the untreated tumors.
Monitor tones down financial restraints on providers of NHS services
Authors: A. O'Dowd
Journal: BMJ (2012)

The possibility that providers of NHS services in England would be tied to strict financial restraints before being given a licence to operate have been toned down in a consultation document from Monitor, the regulator of NHS foundation trusts.1

Monitor published a major consultation on 31 July on its proposed NHS provider licence—the main tool that the regulator would use to regulate providers of NHS services from next year.

The consultation comes after extensive discussions with stakeholders as Monitor developed its proposals over the past year.

Initially, Monitor considered imposing conditions on private companies that provide NHS “commissioner requested services” that meant that companies would have to carry on providing these services even if they proved not to be profitable; services would still have …
Elective high-frequency oscillatory versus conventional ventilation in preterm infants: a systematic review and meta-analysis of individual patients' data
Authors: Filip Cools, Lisa M Askie, Martin Offringa, Jeanette M Asselin, Sandra A Calvert, Sherry E Courtney, Carlo Dani, David J Durand, Dale R Gerstmann, David J Henderson-Smart, Neil Marlow, Janet L Peacock, J Jane Pillow, Roger F Soll, Ulrich H Thome, Patrick Truffert, Michael D Schreiber, Patrick Van Reempts, Valentina Vendettuoli, Giovanni Vento
Journal: The Lancet (2010)
Fibroblast growth factor-21 protects human skeletal muscle myotubes from palmitate-induced insulin resistance by inhibiting stress kinase and NF-κB
Authors: Min Suk Lee, Sung-E Choi, Eun Suk Ha, So-Yeon An, Tae Ho Kim, Seung Jin Han, Hae Jin Kim, Dae Jung Kim, Yup Kang, Kwan-Woo Lee
Journal: Metabolism (2012)
Chest wall and lung contribution to the elastic properties of the respiratory system in patients with chronic obstructive pulmonary disease
Authors: VM Ranieri, R Giuliani, L Mascia, S Grasso, V Petruzzelli, F Bruno, T Fiore, A Brienza
Journal: European Respiratory Journal (1996)

Conflicting data are available on the relative contribution of the chest wall (cw) to the intrinsic positive end-expiratory pressure of the total respiratory system (PEEPi,rs) in patients with chronic obstructive pulmonary disease (COPD). In order to assess the chest wall and lung contribution to the elastic properties of the respiratory system in COPD patients during acute ventilatory failure, using the "interrupter technique", static inflation volume-pressure (V-P) curves of the total respiratory system (rs), lung (L) and cw were obtained in seven mechanically-ventilated COPD patients during application of zero end-expiratory pressure (ZEEP) and different levels (0-15 cmH2O) of PEEP. On ZEEP, PEEPi,rs was present in all patients (range 10.5-13.1 cmH2O), to which PEEPi,cw and PEEPi,L contributed 17 +/- 2 and 83 +/- 1%, respectively. The static V-P curves of the rs, L, and cw on ZEEP were concave toward the horizontal axis, indicating that elastance increased with inflating volume. Application of PEEP did not affect lung and chest wall mechanics until PEEP levels exceeding 90% of PEEPi,cw on ZEEP (critical value of PEEP (Pcrit)). At PEEP levels higher than Pcrit, and relative to the V-P curves on ZEEP, we observed that: 1) the V-P curve of the rs showed an initial shift along the curve on ZEEP followed by a downward displacement with inflating volume; 2) the V-P curve of the L was shifted along the curve on ZEEP throughout inflating volume; and 3) the V-P curve of the cw was initially displaced along the curve on ZEEP, whilst a downward displacement appeared at higher lung volume. In conclusion, our data show that, in chronic obstructive pulmonary disease patients with flow limitation, the increase in pleural pressure does not make a significant contribution to the intrinsic positive end-expiratory pressure of the total respiratory system. However, during tidal ventilation, a substantial increase in elastance of the chest wall is present. The critical values of positive end-expiratory pressure below which there are no changes in chest wall and lung mechanics amount to 90% of the total PEEPi,rs on ZEEP. Positive end-expiratory pressure levels higher than such critical value cause important alterations of the elastic properties of the lung and chest wall.
Prevalence and Correlates of Fatigue in Long-Term Survivors of Childhood Leukemia
Authors: Kathleen A. Meeske, Stuart E. Siegel, Denise R. Globe, Wendy J. Mack, Leslie Bernstein
Journal: Journal of Clinical Oncology (2005)

To estimate the prevalence of fatigue, identify the factors associated with fatigue, and to explore the relationship between fatigue and quality of life (QOL) in long-term survivors of childhood acute lymphoblastic leukemia (ALL).One hundred sixty-one ALL survivors diagnosed at Childrens Hospital Los Angeles (Los Angeles, CA) before age 18 years and between January 1, 1975 and December 31, 1995, participated in a structured telephone interview. Participants were aged 18 to 41 years and off treatment for an average of 14 years. Four measures of fatigue, including the Revised-Piper Fatigue Scale, were used to assess fatigue; depression was assessed using the Center for Epidemiological Studies Depression Scale. Multivariate logistic regression models were developed to identify factors associated with fatigue and depression.Prevalence of fatigue (30%) fell within the general population normal limits. Fatigue and depression were highly correlated (Pearson r = 0.75). Fatigue was associated with marriage (OR = 0.11; 95% CI, 0.02 to 0.50), having children (OR = 5.80; 95% CI, 1.30 to 25.82), sleep disturbances (OR = 6.15; 95% CI, 2.33 to 16.22), pain (OR = 5.56; 95% CI, 2.13 to 14.48), obesity (OR = 3.80; 95% CI, 1.41 to 10.26), cognitive impairment (OR = 2.56; 95% CI, 1.02 to 6.38), and exercise-induced symptoms (OR = 2.98; 95% CI, 1.11 to 8.02). Four factors associated with fatigue were also associated with depression: sleep disturbances, pain, obesity, and cognitive impairment. Fatigue was inversely related to QOL.Some survivors of childhood ALL experience fatigue many years after treatment. Fatigued survivors represent a high-risk subgroup as they report more depression and poorer QOL than non-fatigued survivors and their peers.
Assessment of Myocardial Inflammation Produced by Experimental Coronary Occlusion and Reperfusion With <sup>99m</sup> Tc-RP517, a New Leukotriene B4 Receptor Antagonist That Preferentially Labels Neutrophils In Vivo
Authors: Laurent M. Riou, Mirta Ruiz, Gail W. Sullivan, Joel Linden, Howard Leong-Poi, Jonathan R. Lindner, Thomas D. Harris, George A. Beller, David K. Glover
Journal: Circulation (2002)

Background — 99m Tc-RP517 is a new leukotriene B 4 (LTB4) receptor antagonist developed for imaging acute inflammation or infection. A unique property of 99m Tc-RP517 is its ability to label white blood cells in vivo after intravenous injection. The goals of this study were to determine relative 99m Tc-RP517 binding to human leukocyte subtypes and the 99m Tc-RP517 uptake pattern in canine myocardium where inflammation was induced by either coronary occlusion and reperfusion or tumor necrosis factor α (TNFα) injection. Methods and Results — Fluorescence-activated cell sorter analysis was performed on whole human blood (n=2) and isolated neutrophils (n= 4) with a fluorescent analog of 99m Tc-RP517, [F]-RP517. In whole blood, [F]-RP517 (500 nmol/L) preferentially labeled neutrophils. On isolated neutrophils, [F]-RP517 (10 nmol/L) binding was inhibited by 44% when LTB4 (400 nmol/L) was added. 99m Tc-RP517 was injected intravenously in anesthetized, open-chest dogs before coronary occlusion (90 minutes) and reperfusion (120 minutes) (n=9) or before intramyocardial TNFα injection (n=3). Ex vivo images of heart slices were acquired. The left ventricle was divided into 72 segments for flow and 99m Tc-RP517 uptake analysis. There was an inverse exponential relationship between 99m Tc-RP517 uptake and occlusion flow ( r =0.73). In the same 15 segments, 99m Tc-RP517 uptake was highly correlated with the neutrophil enzyme myeloperoxidase ( r =0.91). Ex vivo images revealed tracer uptake in the reperfused area (ischemic to normal count ratio=2.7±0.2). Conclusions — RP517 binds to the neutrophil LTB4 receptor after intravenous injection. After reperfusion, 99m Tc-RP517 uptake correlated with myeloperoxidase and was observed on ex vivo images, indicating that this tracer may have potential as an inflammation-imaging agent.
Phase III Randomized, Placebo-Controlled, Double-Blind Trial of Risedronate for the Prevention of Bone Loss in Premenopausal Women Undergoing Chemotherapy for Primary Breast Cancer
Authors: Stephanie L. Hines, Betty Anne Mincey, Jeff A. Sloan, Sachdev P. Thomas, Elaine Chottiner, Charles L. Loprinzi, Mark D. Carlson, Pamela J. Atherton, Muhammad Salim, Edith A. Perez
Journal: Journal of Clinical Oncology (2008)

Purpose Risedronate prevents bone loss in postmenopausal women. The purpose of this study was to determine whether risedronate prevents bone loss in premenopausal women undergoing chemotherapy for breast cancer. Patients and Methods Premenopausal women undergoing chemotherapy for breast cancer were treated with oral calcium 600 mg and vitamin D 400 U daily and randomly assigned to receive oral risedronate 35 mg weekly or placebo, with all these therapies beginning within a month of the start of chemotherapy. Most chemotherapy regimens included anthracyclines, taxanes, or cyclophosphamide. Bone mineral density (BMD) was measured at baseline and 1 year. The primary end point was the change in lumbar spine (LS) BMD from baseline to 1 year. Results A total of 216 women enrolled; 170 women provided BMD data at 1 year. There was no difference in the mean change or percent change in LS BMD between groups, with a loss of 4.3% in the risedronate arm and 5.4% for placebo at 1 year (P = .18). Loss of BMD at the femoral neck and total hip were also similar between treatment groups. Risedronate was well tolerated, with no significant differences in adverse events compared with placebo, except that arthralgias and chest pain were worse in those receiving the placebos. Conclusion Risedronate did not prevent bone loss in premenopausal women undergoing adjuvant chemotherapy for breast cancer.