tbuckley/cabot-search huggingface dataset:
Intraperitoneal Chemotherapy in Ovarian Cancer Remains Experimental
Authors: Martin Gore, Andreas du Bois, Ignace Vergote
Journal: Journal of Clinical Oncology (2006)

Furthermore, more patients in the experimental arm (IP chemotherapy) were lost to follow-up, compared with those treated in the control arm (11v five patients). Such differences are not usually a concern. However, there were 127 and 101 patient deaths in the control and IP arms of the trial, respectively, and as few as three additional patient deaths in the IP arm could make the result nonsignificant. The statistical difference between the two arms of the trial is so marginal that these differences in eligiblity or loss of follow-up need to be investigated further. The absolute difference in patients alive (15 patients) was less than those patients lost to follow-up (16 patients; 11 in the IP arm), and this is a very small proportion of the total population. It must be questioned whether such toxic treatment should be introduced as
Abstract 329: Discovery of a Novel Paracrine Angiogenic Factor from Akt-Transduced Mesenchymal Stem Cells for Cell/Protein-based Therapy in angiogenesis
Authors: Jian Guo, Jing Huang, Maria Mirotsou, Hui Mu, Lunan Zhang, David Loiselle, Timothy Haystead, Richard E Pratt, Victor J Dzau
Journal: Circulation (2007)

Previously we have shown that injection of mesenchymal stem cells overexpressing the survival gene Akt (Akt-MSCs) into infarcted rodent hearts dramatically reduced the infarct size and improved ventricular function as early as 72 hours after treatment. Furthermore, injection of conditioned medium isolated from these cells reproduced the similar effects. These data strongly suggest that the observed beneficial effects are due to paracrine factors released from the Akt-MSCs. Since angiogenesis has been shown previously to reduce ischemia injury, we reasoned that part of the protective effects include an angiogenic component. To help identify potential paracrine factors, we performed microarray analysis of Akt-MSCs and identified 46 novel differentially expressed transcripts, and among these, 5 novel transcripts potentially encoding secreted proteins were identified. The open reading frames of these novel transcripts were cloned and expressed in E. coli as maltose binding protein (MBP) fusion proteins. These 5 novel MBP fusion proteins (10nM) were tested in an endothelial tube formation assay using Human Umbilical Vein Endothelial Cells (HUVECs). Compared to MBP control or fresh serum free media, one of the MBP-novel fusion proteins has a pronounced tube forming ability (n = 8, p &lt; 0.001). Bioinformatic analysis reveals that this novel angiogenic factor contains two fibronectin type III domains and a short hydrophobic ~20 amino acid as the signal peptide at amino-terminus. Full-length human cDNA (1704 base pairs) of this novel angiogenic factor was cloned into pcDNA-DEST40 plasmid without the stop codon, in the translational frame fused with V5-epitope at the carboxyl terminus. Upon transient transfection into HEK293 cells with this expression construct, this novel angiogenic factor secreted into culture medium as ~63 KDa protein evidenced by western blotting using anti-V5 antibody. Further studies will dissect the signaling mechanisms of this novel factor and our ongoing in vivo studies will further explore the possibilities of using protein and/or cell-based approach for novel therapeutic angiogenesis for the injured heart.
One Step Ahead of the Game: Viral Immunomodulatory Molecules
Authors: Melanie K. Spriggs
Journal: Annual Review of Immunology (1996)

For decades cell biologists have relied on viruses to facilitate the study of complex cellular function. More recently, the tragedy of the AIDS epidemic has focused considerable human and financial resources on both virology and immunology, resulting in the generation of new information relating these disciplines. As the miracle of the mammalian immune system unfolds in the laboratory, the elegance of the mechanisms used by co-evolving viruses to circumvent detection and destruction by the host becomes inescapably obvious. Although many observations of virus-induced phenomena that likely contribute to the virus's escape of immune surveillance are still empirical, many other such phenomena have now been defined at the molecular level and confirmed in in vivo models. Immune modulators encoded within viral genomes include proteins that regulate antigen presentation, function as cytokines or cytokine antagonists, inhibit apoptosis, and interrupt the complement cascade. The identification of such gene products and the elucidation of their function have substantially strengthened our understanding of specific virus-host interactions and, unexpectedly, have contributed to the recognition of potent synergy between viruses, which can result in an unpredictable exacerbation of disease in co-infected individuals. Because many viral immune modulators clearly have host counterparts, viruses provide a valuable method for studying normal immune mechanisms. It is conceivable that an improved understanding of virus-encoded immunomodulators will enhance our ability to design reagents for use in therapeutic intervention in disease and in vaccine development.
Abstract 736: DJ4, a novel ROCK and MRCK inhibitor, potently inhibits migration and invasion of cancer cells
Authors: Vijaykumar P. Kale, Dhimant Desai, Taryn Dick, Katherine Choe, Ashley Colledge, Shantu Amin, Jeremy Hengst, Jong Yun
Journal: Cancer Research (2014)

Abstract Rho-associated coiled-coil containing protein kinase (Rho kinase/ROCK) and myotonic dystrophy kinase-related Cdc42-binding kinase (MRCK) are involved in the aggressive migration of cancer cells. These are the key proteins involved in the formation of stress fibers that confer contractility to cancer cells during migration and invasion. ROCK and MRCK are primarily involved in amoeboid and mesenchymal type of migration of cancer cells respectively. Earlier studies reported that combined inhibition/silencing of ROCK and MRCK has more pronounced effect than inhibition of the individual kinases suggesting a more effective therapeutic strategy to combat metastatic cancers. With this hypothesis in mind, we developed a series of novel multikinase inhibitors and identified DJ4 as a potent ATP competitive inhibitor of ROCK1, ROCK2 and MRCKβ. DJ4 effectively inhibits the kinase activity of ROCK (ROCK1 and ROCK2) and MRCK in a cell-free system and multiple human non-small cell lung cancer cell lines. In cellular functional assays DJ4 inhibited migration of human melanoma, lung, pancreatic and breast cancer cells in a concentration-dependent manner. In live cell imaging over 20h by time-lapse microscopy, DJ4 (2.5µM ) reduced the migration rate of lung-and breast-cancer cells by 2.7 and 5.5 times compared to control cells respectively. DJ4 (5µM) also inhibited invasion of MDA-MB-231 breast cancer cells by ∼70%. Fluorescent microscopic observation also revealed that inhibition of activity of these kinases, by DJ4, causes reduction in stress fibers which leads to inhibition of cell contractility and migration. In summary, our studies demonstrate that DJ4 is a potent ATP competitive inhibitor of ROCK and MRCK, and effectively inhibits migration and invasion of multiple cancers in vitro. Together these results indicate that DJ4 has a strong potential to be an anti-metastatic drug against multiple cancer types. Citation Format: Vijaykumar P. Kale, Dhimant Desai, Taryn Dick, Katherine Choe, Ashley Colledge, Shantu Amin, Jeremy Hengst, Jong Yun. DJ4, a novel ROCK and MRCK inhibitor, potently inhibits migration and invasion of cancer cells. [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 736. doi:10.1158/1538-7445.AM2014-736
Bone Marrow Transplantation for Recessive Dystrophic Epidermolysis Bullosa
Authors: John E Wagner, Akemi Ishida-Yamamoto, John A McGrath, Maria Hordinsky, Douglas R Keene, David T Woodley, Mei Chen, Megan J Riddle, Mark J Osborn, Troy Lund, Michelle Dolan, Bruce R Blazar, Jakub Tolar
Journal: New England Journal of Medicine (2010)

Recessive dystrophic epidermolysis bullosa is an incurable, often fatal mucocutaneous blistering disease caused by mutations in COL7A1, the gene encoding type VII collagen (C7). On the basis of preclinical data showing biochemical correction and prolonged survival in col7 −/− mice, we hypothesized that allogeneic marrow contains stem cells capable of ameliorating the manifestations of recessive dystrophic epidermolysis bullosa in humans.Between October 2007 and August 2009, we treated seven children who had recessive dystrophic epidermolysis bullosa with immunomyeloablative chemotherapy and allogeneic stem-cell transplantation. We assessed C7 expression by means of immunofluorescence staining and used transmission electron microscopy to visualize anchoring fibrils. We measured chimerism by means of competitive polymerase-chain-reaction assay, and documented blister formation and wound healing with the use of digital photography.One patient died of cardiomyopathy before transplantation. Of the remaining six patients, one had severe regimen-related cutaneous toxicity, with all having improved wound healing and a reduction in blister formation between 30 and 130 days after transplantation. We observed increased C7 deposition at the dermal-epidermal junction in five of the six recipients, albeit without normalization of anchoring fibrils. Five recipients were alive 130 to 799 days after transplantation; one died at 183 days as a consequence of graft rejection and infection. The six recipients had substantial proportions of donor cells in the skin, and none had detectable anti-C7 antibodies.Increased C7 deposition and a sustained presence of donor cells were found in the skin of children with recessive dystrophic epidermolysis bullosa after allogeneic bone marrow transplantation. Further studies are needed to assess the long-term risks and benefits of such therapy in patients with this disorder. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00478244.)
Molecular single-cell analysis of the clonal relationship of small Epstein-Barr virus–infected cells and Epstein-Barr virus–harboring Hodgkin and Reed/Sternberg cells in Hodgkin disease
Authors: Tilmann Spieker, Julia Kurth, Ralf Küppers, Klaus Rajewsky, Andreas Bräuninger, Martin-Leo Hansmann
Journal: Blood (2000)
Cytosolic PLA2 is required for CTL-mediated immunopathology of celiac disease via NKG2D and IL-15
Authors: Fangming Tang, Zhangguo Chen, Cezary Ciszewski, Mala Setty, Jason Solus, Maria Tretiakova, Ellen Ebert, Jin Han, Anning Lin, Stefano Guandalini, Veronika Groh, Thomas Spies, Peter Green, Bana Jabri
Journal: The Journal of Experimental Medicine (2009)

IL-15 and NKG2D promote autoimmunity and celiac disease by arming cytotoxic T lymphocytes (CTLs) to cause tissue destruction. However, the downstream signaling events underlying these functional properties remain unclear. Here, we identify cytosolic phospholipase A2 (cPLA2) as a central molecule in NKG2D-mediated cytolysis in CTLs. Furthermore, we report that NKG2D induces, upon recognition of MIC+ target cells, the release of arachidonic acid (AA) by CTLs to promote tissue inflammation in association with target killing. Interestingly, IL-15, which licenses NKG2D-mediated lymphokine killer activity in CTLs, cooperates with NKG2D to induce cPLA2 activation and AA release. Finally, cPLA2 activation in intraepithelial CTLs of celiac patients provides an in vivo pathophysiological dimension to cPLA2 activation in CTLs. These results reveal an unrecognized link between NKG2D and tissue inflammation, which may underlie the emerging role of NKG2D in various immunopathological conditions and define new therapeutic targets.
Myeloproliferative neoplasm patient symptom burden and quality of life: Evidence of significant impairment compared to controls
Authors: Lesley A. Anderson, Glen James, Andrew S. Duncombe, Ruben Mesa, Robyn Scherber, Amylou C. Dueck, Frank de Vocht, Mike Clarke, Mary F. McMullin
Journal: American Journal of Hematology (2015)

The myeloproliferative neoplasms (MPN) including polycythaemia vera (PV), essential thrombocythaemia and primary myelofibrosis (PMF) are rare diseases contributing to significant morbidity. Symptom management is a prime treatment objective but current symptom assessment tools have not been validated compared to the general population. The MPN-symptom assessment form (MPN-SAF), a reliable and validated clinical tool to assess MPN symptom burden, was administered to MPN patients (n = 106) and, for the first time, population controls (n = 124) as part of a UK case-control study. Mean symptom scores were compared between patients and controls adjusting for potential confounders. Mean patient scores were compared to data collected by the Mayo Clinic, USA on 1,446 international MPN patients to determine patient group representativeness. MPN patients had significantly higher mean scores than controls for 25 of the 26 symptoms measured (P < 0.05); fatigue was the most common symptom (92.4% and 78.1%, respectively). Female MPN patients suffered worse symptom burden than male patients (P < 0.001) and substantially worse burden than female controls (P < 0.001). Compared to the Mayo clinic patients, MPN-UK patients reported similar symptom burden but lower satiety (P = 0.046). Patients with PMF reported the worst symptom burden (88.3%); significantly higher than PV patients (P < 0.001). For the first time we report quality of life was worse in MPN-UK patients compared with controls (P < 0.001).
Demonstration of Cellular Antigens on Sarcoma Cells by an Indirect&lt;sup&gt;125&lt;/sup&gt; I-Labeled Antibody Technique&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Felix H. Harder, Charles F. McKhann
Journal: JNCI Journal of the National Cancer Institute (1968)

An indirect, isotope-labeled antibody technique was developed to demonstrate antigen-antibody interactions in vitro with cells that do not ordinarily undergo a cytotoxic reaction. With125I-labeled goat anti-mouse immunoglobulin, it was possible to demonstrate absorption of mouse antibodies directed against normal H-2 antigens on the surface of normal lymphoid cells, sarcoma cells growing in the ascites form, and sarcoma cells prepared from trypsinized portions of solid tumor. Tumor-specific antigens were demonstrated on cells of a Friend virus-induced lymphoma and a methylcholanthrene-induced sarcoma. In the latter instance, mice with transplants of the tumors from isologous mice had significant levels of circulating antibody only after the immunizing tumor was excised.
Edoxaban Effects on Bleeding Following Punch Biopsy and Reversal by a 4-Factor Prothrombin Complex Concentrate
Authors: Hamim Zahir, Karen S. Brown, Alexander G. Vandell, Madhuri Desai, Jen-Fue Maa, Victor Dishy, Barbara Lomeli, Annette Feussner, Wenqin Feng, Ling He, Michael A. Grosso, Hans J. Lanz, Elliott M. Antman
Journal: Circulation (2014)

Background— The oral factor Xa inhibitor edoxaban has demonstrated safety and efficacy in stroke prevention in patients with atrial fibrillation and in the treatment and secondary prevention of venous thromboembolism. This study investigated the reversal of edoxaban’s effects on bleeding measures and biomarkers by using a 4-factor prothrombin complex concentrate (4F-PCC). Methods and Results— This was a phase 1 study conducted at a single site. This was a double-blind, randomized, placebo-controlled, 2-way crossover study to determine the reversal effect of descending doses of 4F-PCC on bleeding duration and bleeding volume following edoxaban treatment. A total of 110 subjects (17 in part 1, 93 in part 2) were treated. Intravenous administration of 4F-PCC 50, 25, or 10 IU/kg following administration of edoxaban (60 mg) dose-dependently reversed edoxaban’s effects on bleeding duration and endogenous thrombin potential, with complete reversal at 50 IU/kg. Effects on prothrombin time were partially reversed at 50 IU/kg. A similar trend was seen for bleeding volume. Conclusions— The 4F-PCC dose-dependently reversed the effects of edoxaban (60 mg), with complete reversal of bleeding duration and endogenous thrombin potential and partial reversal of prothrombin time following 50 IU/kg. Edoxaban alone and in combination with 4F-PCC was safe and well tolerated in these healthy subjects. A dose of 50 IU/kg 4F-PCC may be suitable for reversing edoxaban anticoagulation. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT02047565.
Body Weight and Mortality Among Men and Women in China
Authors: Dongfeng Gu, Jiang He, Xiufeng Duan, Kristi Reynolds, Xigui Wu, Jing Chen, Guangyong Huang, Chung-Shiuan Chen, Paul K Whelton
Journal: JAMA (2006)

ContextThe effect of underweight and obesity on mortality has not been well characterized in Asian populations.ObjectiveTo examine the relationship between body mass index (BMI) and mortality in Chinese adults.Design, Setting, and ParticipantsA prospective cohort study in a nationally representative sample of 169 871 Chinese men and women aged 40 years or older. Data on body weight and covariables were obtained at a baseline examination in 1991 using a standard protocol. Follow-up evaluation was conducted in 1999-2000, with a response rate of 93.4% (n = 158 666).Main Outcome MeasuresBody mass index and all-cause mortality.ResultsAfter excluding those participants with missing body weight or height values, 154 736 adults were included in the analysis. After adjustment for age, sex, cigarette smoking, alcohol consumption, physical activity, education, geographic region (north vs south), and urbanization (urban vs rural), a U-shaped association between BMI and all-cause mortality was observed (P&lt;.001). Using those participants with a BMI of 24.0 to 24.9 as the reference group, the relative risks of all-cause mortality across categories of BMI were 1.65 (95% confidence interval [CI], 1.54-1.77) for BMI less than 18.5, 1.31 (95% CI, 1.22-1.41) for BMI 18.5 to 19.9, 1.20 (95% CI, 1.11-1.29) for BMI 20.0 to 20.9, 1.12 (95% CI, 1.04-1.21) for BMI 21.0 to 21.9, 1.11 (95% CI, 1.03-1.20) for BMI 22.0 to 22.9, 1.09 (95% CI, 1.01-1.19) for BMI 23.0 to 23.9, 1.00 (95% CI, 0.92-1.08) for BMI 25.0 to 26.9, 1.15 (95% CI, 1.06-1.24) for BMI 27.0 to 29.9, and 1.29 (95% CI, 1.16-1.42) for BMI 30.0 or more. The U-shaped association existed even after excluding participants who were current or former smokers, heavy alcohol drinkers, or who had prevalent chronic illness at the baseline examination, or who died during the first 3 years of follow-up. A similar association was observed between BMI and mortality from cardiovascular disease, cancer, and other causes.ConclusionsOur results indicate that both underweight and obesity were associated with increased mortality in the Chinese adult population. Furthermore, our findings support the use of a single common recommendation for defining overweight and obesity among all racial and ethnic groups.
Successful Treatment of Renal Cell Carcinoma With Sorafenib After Effective but Hepatotoxic Sunitinib Exposure
Authors: Hans M. Westgeest, Nielka P. van Erp, Richard J. Honeywell, Ronald Hoekstra, Godefridus J. Peters, Henk M.W. Verheul
Journal: Journal of Clinical Oncology (2012)
Israeli army accused of obstructing medical access to civilians
Authors: Owen Dyer
Journal: BMJ (2004)

Medecins Sans Frontieres (MSF) has accused the Israeli army of obstructing medical access to civilians in the Rafah refugee camp, occupied since last week by Israeli forces.

Nasira Butin, local medical coordinator for the charity, said: “Our teams have experienced enormous problems in reaching health centres and parts of town that have come under attack. There seems to be hardly any coordination among the Israeli authorities on the ground, and our teams, though officially authorised to travel, are having guns pointed at them and their path blocked by tanks. …
NICE says doctors should identify people at high risk of contracting sexually transmitted infections
Authors: Susan Mayor
Journal: BMJ (2007)

The National Institute for Health and Clinical Excellence has recommended that health professionals should identify people at high risk of contracting sexually transmitted infections, determined on the basis of their sexual history, and arrange one to one discussions to reduce their risk.

The guidance on sexual health suggests using a wide range of opportunities for assessing risk of infections, including when discussing contraception, pregnancy, or abortion; carrying out a cervical smear test, offering a test …
Preconditioning: state of the art myocardial protection
Authors: C. S Lawson, J. M Downey
Journal: Cardiovascular Research (1993)

Journal Article Preconditioning: state of the art myocardial protection Get access Clive S Lawson, Clive S Lawson Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London SEl, United Kingdom: C S Lawson; Department of Physiology, University of South Alabama, Mobile, Alabama, USA: J M Downey. Correspondence to Dr Lawson, at: Department of Cardiology, The London Chest Hospital, Bonner Road, London E2 9JX, United Kingdom. Search for other works by this author on: Oxford Academic PubMed Google Scholar James M Downey James M Downey Cardiovascular Research, The Rayne Institute, St Thomas' Hospital, London SEl, United Kingdom: C S Lawson; Department of Physiology, University of South Alabama, Mobile, Alabama, USA: J M Downey. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 27, Issue 4, April 1993, Pages 542–550, https://doi.org/10.1093/cvr/27.4.542 Published: 01 April 1993 Article history Received: 16 October 1992 Accepted: 02 February 1993 Published: 01 April 1993
Effects of quitting cannabis on respiratory symptoms
Authors: Robert J. Hancox, Hayden H. Shin, Andrew R. Gray, Richie Poulton, Malcolm R. Sears
Journal: European Respiratory Journal (2015)

Smoking cannabis is associated with symptoms of bronchitis. Little is known about the persistence of symptoms after stopping cannabis use. We assessed associations between changes in cannabis use and respiratory symptoms in a population-based cohort of 1037 young adults. Participants were asked about cannabis and tobacco use at ages 18, 21, 26, 32 and 38 years. Symptoms of morning cough, sputum production, wheeze, dyspnoea on exertion and asthma diagnoses were ascertained at the same ages. Frequent cannabis use was defined as ≥52 occasions over the previous year. Associations between frequent cannabis use and respiratory symptoms were analysed using generalised estimating equations with adjustments for tobacco smoking, asthma, sex and age. Frequent cannabis use was associated with morning cough (OR 1.97, p&lt;0.001), sputum production (OR 2.31, p&lt;0.001) and wheeze (OR 1.55, p&lt;0.001). Reducing or quitting cannabis use was associated with reductions in the prevalence of cough, sputum and wheeze to levels similar to nonusers. Frequent cannabis use is associated with symptoms of bronchitis in young adults. Reducing cannabis use often leads to a resolution of these symptoms.
Relationship among mental stress–induced ischemia and ischemia during daily life and during exercise: the Psychophysiologic Investigations of Myocardial Ischemia (PIMI) Study
Authors: Peter H Stone, David S Krantz, Robert P McMahon, A.David Goldberg, Lewis C Becker, Bernard R Chaitman, Herman A Taylor, Jerome D Cohen, Kenneth E Freedland, Barry D Bertolet, Cecil Coughlan, Carl J Pepine, Peter G Kaufmann, David S Sheps
Journal: Journal of the American College of Cardiology (1999)
Achieving GINA/NIH guideline-based asthma control with salmeterol/fluticasone compared with fluticasone alone*1The results of the GOAL study
Authors: W.W. Busse, E. Bateman, H. Boushey, J. Bousquet, T. Clark, R. Pauwels, S. Pedersen
Journal: Journal of Allergy and Clinical Immunology (2004)