tbuckley/cabot-search huggingface dataset:
Overexpression of the Centrosomal Protein Aurora-A Kinase is Associated with Poor Prognosis in Epithelial Ovarian Cancer Patients
Authors: Charles N. Landen, Yvonne G. Lin, Anand Immaneni, Michael T. Deavers, William M. Merritt, Whitney A. Spannuth, Diane C. Bodurka, David M. Gershenson, William R. Brinkley, Anil K. Sood
Journal: Clinical Cancer Research (2007)

Abstract Purpose: To assess the clinical significance of Aurora-A kinase, a centrosome-regulating serine-threonine kinase, in ovarian carcinoma. Experimental Design: Aurora-A kinase expression was assessed by Western blot (cell lines) or immunohistochemistry (high-grade epithelial ovarian cancers), and clinical variables were collected by retrospective chart review. Centrosome amplification was assessed by immunofluorescence in cell lines, and by immunohistochemistry in patient samples. Results: All ovarian cancer cell lines exhibited significant Aurora-A kinase protein overexpression, and all except A2780-par had centrosome amplification, a characteristic of mitotic dysregulation leading to genomic instability. Fifty-eight of 70 patient samples (82.8%) exhibited Aurora-A kinase overexpression compared with normal ovarian surface epithelium. High Aurora-A kinase expression was strongly associated with supernumerary centrosome count in tumor cells (P &amp;lt; 0.001). Tumors with the greatest Aurora-A overexpression (n = 24) had decreased patient survival (median survival, 1.44 versus 2.81 years; P = 0.01). High Aurora-A expression and suboptimal surgical cytoreduction remained predictors of poor survival (P &amp;lt; 0.05) by multivariate analysis. Conclusions: Aurora-A kinase is overexpressed by a substantial proportion of ovarian cancers and is associated with centrosome amplification and poor survival. It may be a useful prognostic marker and target in ovarian cancer.
Cancer Patients' and Patient Advocates' Perspectives on a Novel Information Source: A Qualitative Study of <i>The Art of Oncology, When the Tumor Is Not the Target</i>
Authors: Kristin S. Vickers, Julie C. Hathaway, Christi A. Patten, Matthew M. Clark, Teresa L. Britt, Sherry A. Looker, Phaedra T. Johnson, Charles L. Loprinzi
Journal: Journal of Clinical Oncology (2005)

Kristin S. Vickers, Section of Patient Education and Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN Julie C. Hathaway, Section of Patient Education, Mayo Clinic, Rochester, MN Christi A. Patten and Matthew M. Clark, Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN Teresa L. Britt, Nursing Research, Mayo Clinic, Rochester, MN Sherry A. Looker, Department of Medical Oncology, Mayo Clinic, Rochester, MN Phaedra T. Johnson, Department of Psychology, University of Wisconsin-Stout, Menomonie, WI Charles L. Loprinzi, Department of Medical Oncology, Mayo Clinic, Rochester, MN
AFRICAN AMERICAN RACE IS A CORRELATE OF HEART FAILURE IN BREAST CANCER SURVIVORS: A STUDY OF 26,347 WOMEN IDENTIFIED WITH BREAST CANCER FROM 1973-2007
Authors: Anna Liza Valina-Toth, Theresa Zavodnik, Sinziana Seicean, Juan Plana, Thomas Marwick
Journal: Journal of the American College of Cardiology (2013)
Betamethasone enemata in ulcerative colitis
Authors: S. G. F. Matts
Journal: Gut (1962)

In this series a very large therapeutic dose of corticosteroid was administered by retention enemata. For the first week the author gave the equivalent of between 300 and 750 mg. of cortisone daily and for the next three weeks 150 to 375 mg. daily. The results were excellent but systemic effects were noted in all who received more than the smallest dose used.
Early Posttransplant Serum Osteoprotegerin Levels Predict Long-Term (8-Year) Patient Survival and Cardiovascular Death in Renal Transplant Patients
Authors: Jøran Hjelmesæth, Thor Ueland, Allan Flyvbjerg, Jens Bollerslev, Torbjørn Leivestad, Trond Jenssen, Troels Krarup Hansen, Steffen Thiel, Solbjørg Sagedal, Jo Røislien, Anders Hartmann
Journal: Journal of the American Society of Nephrology (2006)

The primary objectives of this analysis were to examine the effects of early posttransplantation (10 wk) serum levels of osteoprotegerin (OPG), mannose-binding lectin (MBL), and MBL-associated serine proteases (MASP; MASP-2 and MASP-3) on long-term (8-yr) patient survival, graft survival, and cardiovascular (CV) death. During a period of 16 mo (1995 to 1996), a total of 173 consecutive renal transplant recipients without diabetes before transplantation were included in a prospective study that was designed to address the impact of metabolic CV risk factors on survival and CV end points. Baseline sera from 172 patients were available for analysis. Follow-up data until January 1, 2004, were obtained from a national renal registry. Patients with high (fourth quartile) serum levels of OPG had significantly higher all-cause mortality (hazard ratio [HR] 6.3; 95% confidence interval [CI] 3.3 to 11.8; P<0.001) and CV death (HR 10.8; 95% CI 3.8 to 30.4; P<0.001) than patients with lower OPG concentrations. After multiple Cox regression analysis, high serum levels of OPG remained an independent predictor of all-cause mortality (HR 6.0; 95% CI 3.1 to 11.6, P<0.001) and CV death (HR 8.2; 95% CI 2.5 to 26.4; P<0.001). Multiple linear regression analysis revealed that age, creatinine clearance, and high-sensitivity C-reactive protein all were independently associated with OPG (R2=0.42). No significant association between OPG and death-censored graft loss was revealed. Serum levels of MBL, MASP-2, and MASP-3 were not significantly associated with patient survival, CV death, or graft loss. Early measured posttransplantation serum OPG is a highly significant independent predictor of death from any cause or CV death in white renal transplant recipients.
Chemical Genomics Identifies the Unfolded Protein Response as a Target for Selective Cancer Cell Killing during Glucose Deprivation
Authors: Sakae Saito, Aki Furuno, Junko Sakurai, Asami Sakamoto, Hae-Ryong Park, Kazuo Shin-ya, Takashi Tsuruo, Akihiro Tomida
Journal: Cancer Research (2009)

Glucose deprivation, a cell condition that occurs in solid tumors, activates the unfolded protein response (UPR). A key feature of the UPR is the transcription program activation, which allows the cell to survive under stress conditions. Here, we show that the UPR transcription program is disrupted by the antidiabetic biguanides metformin, buformin, and phenformin depending on cellular glucose availability. These drugs inhibit production of the UPR transcription activators XBP1 and ATF4 and induce massive cell death during glucose deprivation as did the antitumor macrocyclic compound versipelostatin. Gene expression profiling shows remarkable similarity in the modes of action of biguanides and versipelostatin determined by the broad range of glucose deprivation-inducible genes. Importantly, during glucose deprivation, most of the biguanide suppression genes overlap with the genes induced by tunicamycin, a chemical UPR inducer. Gene expression profiling also identifies drug-driven signatures as a tool for discovering pharmacologic UPR modulators. Our findings show that disrupting the UPR during glucose deprivation could be an attractive approach for selective cancer cell killing and could provide a chemical genomic basis for developing UPR-targeting drugs against solid tumors.
Effects of dehydroepiandrosterone on fatigue and well-being in women with quiescent systemic lupus erythematosus: a randomised controlled trial
Authors: A Hartkamp, R Geenen, G L R Godaert, M Bijl, J W J Bijlsma, R H W M Derksen
Journal: Annals of the Rheumatic Diseases (2009)

Objective Dehydroepiandrosterone (DHEA) has been reported to improve fatigue and reduced well-being. Both are major problems in patients with systemic lupus erythematosus (SLE), even with quiescent disease. Low serum DHEA levels are common in SLE. The present work investigates the effects of DHEA administration on fatigue, well-being and functioning in women with inactive SLE. Methods In a double-blind, randomised, placebo-controlled study, 60 female patients with inactive SLE received 200 mg oral DHEA or placebo. Primary outcome measures were general fatigue, depressive mood, mental well-being and physical functioning. Assessments were made before treatment, after 3, 6 and 12 months on medication, and 6 months after cessation of treatment. Results Patients from the DHEA and placebo group improved on general fatigue (p&lt;0.001) and mental well-being (p=0.04). There was no differential effect of DHEA. The belief that DHEA had been used was a stronger predictor for improvement of general fatigue than the actual use of DHEA (p=0.04). Conclusions The trial does not indicate an effect of daily 200 mg oral DHEA on fatigue and well-being, and therefore DHEA treatment is not recommended in unselected female patients with quiescent SLE. Clinical Trials Registration Number NCT00391924
Prolonged bronchoprotection against inhaled methacholine by inhaled BI 1744, a long-acting β2-agonist, in patients with mild asthma
Authors: Paul M. O'Byrne, Just van der Linde, Donald W. Cockcroft, Gail M. Gauvreau, John D. Brannan, Mark FitzGerald, Richard M. Watson, Joanne Milot, Beth Davis, Megan O'Connor, Lorna Hart, Lawrence Korducki, Alan L. Hamilton, Louis-Philippe Boulet
Journal: Journal of Allergy and Clinical Immunology (2009)
An Outpatient Setting for Treating Chronically Ill Psychiatric Patients
Authors: RICHARD T. RADA, ROBERT S. DANIELS, EDGAR DRAPER
Journal: American Journal of Psychiatry (1969)

The relative neglect of the chronically ill psychiatric patient in community mental health planning emphasizes the need for new treatment methods and resources. This paper presents an eight-year experimental application of psychoanalytic principles in an outpatient clinic with a form of therapy (termed "adaptive psychotherapy") specifically designed for the treatment of the chronically ill psychiatric patient. The advantages of this clinic for the training of mental health professionals are also discussed.
NCCN Molecular Testing White Paper: Effectiveness, Efficiency, and Reimbursement
Authors: Paul F. Engstrom, Mara G. Bloom, George Daniel Demetri, Phillip G. Febbo, William Goeckeler, Marc Ladanyi, Bryan Loy, Kate Murphy, Michael Nerenberg, Paul Papagni, Mark Robson, Robert W. Sweetman, Sean Tunis, Jessica DeMartino, Jonathan K. Larsen
Journal: Journal of the National Comprehensive Cancer Network (2011)

Personalized medicine in oncology is maturing and evolving rapidly, and the use of molecular biomarkers in clinical decision-making is growing. This raises important issues regarding the safe, effective, and efficient deployment of molecular tests to guide appropriate care, specifically regarding laboratory-developed tests and companion diagnostics. In May 2011, NCCN assembled a work group composed of thought leaders from NCCN Member Institutions and other organizations to identify challenges and provide guidance regarding molecular testing in oncology and its corresponding utility from clinical, scientific, and coverage policy standpoints. The NCCN Molecular Testing Work Group identified challenges surrounding molecular testing, including health care provider knowledge, determining clinical utility, coding and billing for molecular tests, maintaining clinical and analytic validity of molecular tests, efficient use of specimens, and building clinical evidence.
Gonadal function in Hodgkin's disease: long-term follow-up of chemotherapy.
Authors: J H Waxman, Y A Terry, P F Wrigley, J S Malpas, L H Rees, G M Besser, T A Lister
Journal: BMJ (1982)

A long-term study of gonadal function was conducted in 46 men and 28 women in prolonged remission of advanced Hodgkin9s disease after cyclical combination chemotherapy with nitrogen mustard, vinblastine, prednisolone, and procarbazine. The mean follow-up was 6.9 years. Azoospermia or profound oligospermia occurred in 36 of the men, but late recovery was occasionally observed. Testosterone secretion was preserved. Amenorrhoea and gonadal hormone deficiency developed in 22 of the women and never recovered. Partial or complete chemical sterilisation and gonadal hormone deficiency is currently a consequence of cure of advanced Hodgkin9s disease in most patients.
Heparin Displaces Interferon-γ–Inducible Chemokines (IP-10, I-TAC, and Mig) Sequestered in the Vasculature and Inhibits the Transendothelial Migration and Arterial Recruitment of T Cells
Authors: Hooman Ranjbaran, Yinong Wang, Thomas D. Manes, Alexander O. Yakimov, Shamsuddin Akhtar, Martin S. Kluger, Jordan S. Pober, George Tellides
Journal: Circulation (2006)

Heparin, used clinically as an anticoagulant, also has antiinflammatory properties and has been described to inhibit interferon (IFN)-gamma responses in endothelial cells. We investigated the effects of heparin on the IFN-gamma-inducible chemokines IP-10/CXCL10, I-TAC/CXCL11, and Mig/CXCL9, which play important roles in the vascular recruitment of IFN-gamma-producing Th1 cells through interactions with their cognate receptor, CXCR3.Patients undergoing coronary artery bypass grafting were studied because coronary atherosclerosis is recognized as a Th1-type inflammatory disease and the subjects required systemic heparinization. Plasma levels of IP-10, I-TAC, and Mig increased immediately after heparin administration and diminished promptly after heparin antagonism with protamine. These effects were independent of detectable circulating IFN-gamma or the IFN-gamma inducer interleukin-12. We confirmed previous reports that heparin inhibits the IFN-gamma-dependent production of CXCR3 chemokine ligands using atherosclerotic coronary arteries in organ culture. In addition to prolonged treatment decreasing chemokine secretion, heparin rapidly displaced membrane-associated IP-10 from cultured endothelial cells that did not express CXCR3 and reduced the IP-10-dependent transendothelial migration of T helper cells under conditions of venular shear stress. Finally, heparin administration to immunodeficient mouse hosts decreased both the recruitment and accumulation of memory T cells within allogeneic human coronary arteries.Besides inhibiting IFN-gamma responses, heparin has further immunomodulatory effects by competing for binding with IP-10, I-TAC, and Mig on endothelial cells. Disruption of CXCR3+ Th1 cell trafficking to arteriosclerotic arteries may contribute to the therapeutic efficacy of heparin in inflammatory arterial diseases, and nonanticoagulant heparin derivatives may represent a novel antiinflammatory strategy.
Mononuclear Cell Adherence to Cultured Endothelium Is Enhanced by Hypertension and Insulin Resistance in Healthy Nondiabetic Volunteers
Authors: N.-G. Chen, F. Abbasi, C. Lamendola, T. McLaughlin, J. P. Cooke, P. S. Tsao, G. M. Reaven
Journal: Circulation (1999)

This study was initiated to compare the adherence to cultured endothelial cells of mononuclear cells isolated from normotensive and hypertensive individuals.Mononuclear cell binding to endothelium was greater in patients with hypertension (32+/-1 versus 25+/-2; P<0.001) than in normal volunteers. There was a significant relationship (r=0.42, P<0. 01) between mononuclear cell binding and mean arterial pressure, independent of differences in age, sex, and body mass index. A significant relationship also existed between insulin resistance (estimated by the steady-state plasma glucose concentration during the insulin suppression test) and mononuclear cell binding in both the normotensive (r=0.86, P<0.001) and hypertensive (r=0.74, P<0. 001) groups. Furthermore, multiple regression analysis demonstrated an independent relationship (P<0.001) between mononuclear cell binding and both steady-state plasma glucose and hypertensive status.These results indicate that both hypertension and insulin resistance lead to changes in mononuclear cells that increase their adherence to cultured endothelial cells.
Clinical significance and novel mechanism of action of kallikrein 6 in glioblastoma
Authors: Kristen L. Drucker, Alex R. Paulsen, Caterina Giannini, Paul A. Decker, Sachiko I. Blaber, Michael Blaber, Joon H. Uhm, Brian P. O'Neill, Robert B. Jenkins, Isobel A. Scarisbrick
Journal: Neuro-Oncology (2013)

Kallikreins have prognostic value in specific malignancies, but few studies have addressed their clinical significance to glioblastoma multiforme (GBM). Kallikrein 6 (KLK6) is of potential high relevance to GBM, since it is upregulated at sites of CNS pathology and linked to reactive astrogliosis. Here we examine the clinical value of KLK6 as a prognostic indicator of GBM patient survival and its activity in promoting resistance to cytotoxic agents. The association between patient survival and levels of KLK6 immunoreactivity were investigated in 60 grade IV astrocytoma tumor specimens. Levels of KLK6 RNA were also evaluated in a separate set of GBM patient tumors (n = 23). Recombinant KLK6 or enforced KLK6 overexpression in GBM cell lines was used to evaluate effects on astrocytoma cell survival. A range of KLK6 expression was observed across grade IV tumors, with higher levels a poor prognostic indicator of patient survival (P = .02) even after adjusting for gender and Eastern Cooperative Oncology Group performance scores (P = .01). KLK6 reduced the sensitivity of GBM cell lines to cytotoxic agents, including staurosporine and cisplatin, and to the current standard of patient care: radiotherapy or temozolomide alone or in combination. The ability of KLK6 to promote resistance to apoptosis was dependent on activation of the thrombin receptor, protease activated receptor 1. Taken together, these results indicate that elevated levels of KLK6 in GBM are likely to promote the resistance of tumor cells to cytotoxic agents and are an indicator of reduced patient postsurgical survival times.
Adult-onset renal thrombotic microangiopathy and pulmonary arterial hypertension in cobalamin C deficiency
Authors: Steven Grangé, Soumeya Bekri, Elise Artaud-Macari, Arnaud Francois, Christophe Girault, Anne-Laure Poitou, Ygal Benhamou, Christine Vianey-Saban, Jean-Francois Benoist, Valérie Châtelet, Fabienne Tamion, Dominique Guerrot
Journal: The Lancet (2015)
Variant ALDH2 is associated with accelerated progression of bone marrow failure in Japanese Fanconi anemia patients
Authors: Asuka Hira, Hiromasa Yabe, Kenichi Yoshida, Yusuke Okuno, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Jun Nakamura, Seiji Kojima, Seishi Ogawa, Keitaro Matsuo, Minoru Takata, Miharu Yabe
Journal: Blood (2013)
SST0001, a Chemically Modified Heparin, Inhibits Myeloma Growth and Angiogenesis via Disruption of the Heparanase/Syndecan-1 Axis
Authors: Joseph P. Ritchie, Vishnu C. Ramani, Yongsheng Ren, Annamaria Naggi, Giangiacomo Torri, Benito Casu, Sergio Penco, Claudio Pisano, Paolo Carminati, Monica Tortoreto, Franco Zunino, Israel Vlodavsky, Ralph D. Sanderson, Yang Yang
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Heparanase promotes myeloma growth, dissemination, and angiogenesis through modulation of the tumor microenvironment, thus highlighting the potential of therapeutically targeting this enzyme. SST0001, a nonanticoagulant heparin with antiheparanase activity, was examined for its inhibition of myeloma tumor growth in vivo and for its mechanism of action. Experimental Design: The ability of SST0001 to inhibit growth of myeloma tumors was assessed using multiple animal models and a diverse panel of human and murine myeloma cell lines. To investigate the mechanism of action of SST0001, pharmacodynamic markers of angiogenesis, heparanase activity, and pathways downstream of heparanase were monitored. The potential use of SST0001 as part of a combination therapy was also evaluated in vivo. Results: SST0001 effectively inhibited myeloma growth in vivo, even when confronted with an aggressively growing tumor within human bone. In addition, SST0001 treatment causes changes within tumors consistent with the compound's ability to inhibit heparanase, including downregulation of HGF, VEGF, and MMP-9 expression and suppressed angiogenesis. SST0001 also diminishes heparanase-induced shedding of syndecan-1, a heparan sulfate proteoglycan known to be a potent promoter of myeloma growth. SST0001 inhibited the heparanase-mediated degradation of syndecan-1 heparan sulfate chains, thus confirming the antiheparanase activity of this compound. In combination with dexamethasone, SST0001 blocked tumor growth in vivo presumably through dual targeting of the tumor and its microenvironment. Conclusions: These results provide mechanistic insight into the antitumor action of SST0001 and validate its use as a novel therapeutic tool for treating multiple myeloma. Clin Cancer Res; 17(6); 1382–93. ©2011 AACR.
The hapten-atopy hypothesis III: the potential role of airborne chemicals
Authors: J.P. McFadden, D.A. Basketter, R.J. Dearman, P. Puangpet, I. Kimber
Journal: British Journal of Dermatology (2013)

One explanation for the large increase in the prevalence of atopic disease in developed countries during the last 50 years is the 'hygiene hypothesis'. This proposes that a reduced exposure to pathogenic microorganisms at a key period(s) during development results in the maintenance or acquisition of an atopic phenotype. Alternatively, or additionally, we have postulated that increased exposure to chemicals generally, and to irritant/haptenic chemicals in particular, during critical windows of maternal pregnancy/early life have also contributed to changes in the prevalence of atopic disease. Having previously reviewed the potential roles of oral and cutaneous exposure to chemicals on the subsequent diagnosis of atopic disease, we here consider possible evidence of a role for exposure to airborne chemicals as a contributory factor in acquired susceptibility to atopic allergy. After controlling for known confounders, five specific maternal occupations during pregnancy have been implicated as being associated with subsequent atopic disease in the offspring. Each of these occupations is characterized by high and persistent exposure to airborne chemicals. High-level exposure to volatile organic compounds in the domestic environment, either during pregnancy or in early life, is also associated with development of childhood atopic disease. Similarly, sustained exposure to airborne chlorinated chemicals from swimming pools during childhood has been associated with the development of atopic allergy. A possible immunological basis for these associations is that exposure to certain airborne chemicals, even at low levels, can result in the delivery of 'danger' signals that, in turn, bias the immune response towards the selective induction or maintenance of preferential T helper 2-type immune responses consistent with the acquisition of allergic sensitization.
Efficacy and safety of TMC125 (etravirine) in treatment-experienced HIV-1-infected patients in DUET-1: 24-week results from a randomised, double-blind, placebo-controlled trial
Authors: José Valdez Madruga, Pedro Cahn, Beatriz Grinsztejn, Richard Haubrich, Jacob Lalezari, Anthony Mills, Gilles Pialoux, Timothy Wilkin, Monika Peeters, Johan Vingerhoets, Goedele de Smedt, Lorant Leopold, Roberta Trefiglio, Brian Woodfall
Journal: The Lancet (2007)