tbuckley/cabot-search huggingface dataset:
Abstract 4016: Serum proteomics uncover possible biomarkers associated with progression of metastatic breast cancer
Authors: Adhari A. AlZaabi, Marc Hansen, Steven Graves
Journal: Cancer Research (2014)

Abstract Despite the recognized advances in the treatment of breast cancer, it still accounts for 15% of all cancer-related deaths. Ninety percent of breast cancer deaths are due to unpredicted metastasis. There is neither successful treatment for metastatic patients nor a specific test to predict or detect secondary lesions. Patients with primary tumor will be either overtreated with cytotoxic side effects or undertreated and risk recurrence. This necessitates the need for personalized treatment, which is hard to offer for such heterogeneous disease. Obstacles in treating breast cancer metastasis are mainly due to the gaps exist in the understanding of the molecular mechanism of metastasis. The linear model of metastasis is supported by several observations that reflect an early crosstalk between the primary and secondary tumor, which in turn makes the secondary microenvironment fertile for the growth of disseminated cells. This communication occurs through circulation and utilizes molecules which have not been identified to date. Identifying such molecules may help in detecting initial stages of tumor colonization and predict the target organ of metastasis. Furthermore, these molecules may help to provide a personalized therapy that aims to tailor treatment according to the biology of the individual tumor. Advances in proteomics allows for more reproducible and sensitive biomarker discovery. Proteomic biomarkers are often more translatable to the clinic compared to biomarkers identified using other -omics approaches. Further, protein biomarkers can be found in biological fluids making them a non invasive way to treat or investigate cancer patients. In this study we are screening serum samples of stage I and stage III breast cancer patients using cLC-MS/MS, with a focus on characterizing the differential expression of small peptide biomarkers. We typically analyze 2500 individual small peptide biomarkers in a single serum sample. Comparisons between different sample types (from stage I and III breast cancer patients in this case) allows for the detection of unique short peptide biomarkers present in one sample type. In our preliminary analysis of 6 patients of each type, we find roughly 64 short peptide biomarkers to be upregulated in patients with metastatic breast cancer. We also see the downregulation of an addition 92 short peptides in these same patients. The serum expression pattern and identity of peptides in metastatic patients may provide clues about the biology underlying tumor cell dissemination and colonization to specific sites. Citation Format: Adhari A. AlZaabi, Marc Hansen, Steven Graves. Serum proteomics uncover possible biomarkers associated with progression of metastatic breast cancer. [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 4016. doi:10.1158/1538-7445.AM2014-4016
CIRCULATING EOSINOPHILS IN CARDIOVASCULAR STRESS
Authors: M H ELLESTAD, J REED
Journal: Annals of Internal Medicine (1952)

Article1 February 1952CIRCULATING EOSINOPHILS IN CARDIOVASCULAR STRESSMYRVIN H. ELLESTAD, M.D., JOSEPH REED, M.D.MYRVIN H. ELLESTAD, M.D., JOSEPH REED, M.D.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-36-2-551 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSince the description by Thorn1 of the eosinophil test for adrenal cortical function and the more general acceptance of Selye's work2 emphasizing the importance of the adrenal steroids in adaptation to all stress, the level of circulating eosinophils has been studied in many disease states.Thorn, Roche, Recant3and others have shown typical responses to anesthesia, surgical procedures, infections, etc., dependent on an intact hypophyseal-adrenal axis. A few counts following coronary occlusion have been reported.4In this study, 44 patients with suspected acute myocardial infarction or congestive failure have been followed with daily eosinophil counts to determine the level of...Bibliography1. ThornForshamPruntyHills GWPHFTAG: A test for adrenal cortical insufficiency, J. A. M. A. 137: 1005, 1948. CrossrefMedlineGoogle Scholar2. Selye H: The general adaptation syndrome and the diseases of adaptation, J. Clin. Endocrinol. 6: 117, 1946. CrossrefGoogle Scholar3. RecantHumeForshamThorn LDMPHGW: Studies on the effects of epinephrine on the pituitary-adrenocortical system, J. Clin. Endocrinol. 10: 187, 1950. CrossrefGoogle Scholar4. Gabrilove JL: Circulating eosinophils following trauma, J. Clin. Endocrinol. 10: 637, 1950. CrossrefGoogle Scholar5. Dunger A: Eine einfache Methode der Zählung der eosinophilen Leukozyten und der praktische Wert dieser Untersuchung, München. med. Wchnschr. 57: 1910, 1942. Google Scholar6. RocheHillsThorn MAGGW: The levels of circulating eosinophils and their response to ACTH in surgery. Their use as an index of adrenal cortical function, Proceedings of First Clinical ACTH Conference, Blakiston, Philadelphia, 1950, p. 55. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication March 24, 1951. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byAnginöse Schmerzen und ihre DifferentialdiagnoseDie NebenniereDer klinische Wert der Nebennierenrindentestung mit Acth und AdrenalinIncreased Urinary Urobilinogen Following Acute Myocardial Infarction 1 February 1952Volume 36, Issue 2_Part_2Page: 551-561KeywordsAcute myocardial infarctionAnesthesiaEosinophilsSteroids ePublished: 1 December 2008 Issue Published: 1 February 1952 PDF downloadLoading ...
Community Based Teaching, by Ed Susan L Deutsch
Authors: J B Cookson
Journal: BMJ (1997)

Ed Susan L Deutsch: American College of Physicians, $34, pp 284 ISBN 0 943126 59 2

There is a revolution in undergraduate medical education in Britain at present. One proposed change is to move much of the teaching from teaching hospitals into the community. Reasons given are the hospitals' case mix, the specialised and highly technical nature of much hospital work, and the rapid throughput of many patients. In the community there is said to be a more appropriate case mix, students rely less on technology and more on basic skills, and …
CSF and plasma beta-casomorphin-like opioid peptides in postpartum psychosis
Authors: L H Lindström, F Nyberg, L Terenius, K Bauer, G Besev, L M Gunne, S Lyrenäs, G Willdeck-Lund, B Lindberg
Journal: American Journal of Psychiatry (1984)

The authors measured opioid receptor-active components in the CSF of 11 women with postpartum psychosis, 11 healthy lactating women, and 16 healthy women who were not lactating. Activity that eluted with 0.2 M acetic acid 0.7-0.9 times the total volume of the column (fraction II activity) was significantly higher in the CSF of both healthy and psychotic women in the puerperium than in that of the lactating women. Very high levels of fraction II activity were seen in four psychotic patients. Material from these patients was further characterized by electrophoresis and high-performance liquid chromatography: The material migrated as bovine beta-casomorphin. Receptor-active material with the same characteristics was also found in the plasma of these four patients. The authors conclude that certain cases of postpartum psychosis are associated with the occurrence in plasma and CSF of unique opioid peptides probably related to bovine beta-casomorphin.
808. Electro-Tranfection of Epstein-Barr Virus LMP-2 Specific TCRs Provides a Non-Viral Means To Transfer Antigen Specific T-Cell Receptors to Activated PBMC Populations
Authors: Bela Denes, Daila S. Gridley, Tatyana Timiryasova, Nadja Fodor, Zsuzsanna Takatsy, Istvan Fodor
Journal: Molecular Therapy (2004)

Live vaccinia viruses (VV) are promising vectors of gene delivery for gene- and immuno-therapy of various human diseases. Safety concerns have initiated development of safer VV strains. We explore an attenuation strategy by further weakening of the Lister vaccine strain via virus-mediated blockade of IFN-dependent cell protection mechanism. Previously, we constructed a Lister vaccine derivative (VVr/g) expressing fused Renilla luciferase and jellyfish GFP reporters, which enable non-invasive monitoring of virus dissemination in live animals. Recently, a VVr/g derivative was constructed (VVr/g8) lacking both IFN-α/β and IFN-γ receptor homologs, and retaining propagation potential in vitro. The safety of the new virus vector was investigated by survival assay and biodistribution in nude mice. High dose (3 × 108 plaque-forming units/animal) of VVr/g8 inoculated into mice showed less pronounced virus dissemination, improved weight gain, and increased survival rate as compared with the VVr/g strain. The data indicate a significant increase in attenuation of the VVr/g8 virus. Immunogenicity of viruses was tested in immunocompetent mice by measuring humoral and cell-mediated immune responses utilizing three different methods. Various versions of virus neutralization assay were applied, and none of them showed significant differences between parental Lister, VVr/g and VVr/g8 strains. Quantification of virus-induced 3H-thymidine incorporation, mitogen-induced IFN-γ production, and T lymphocyte subsets by flow cytometry demonstrated similar or greater levels of leukocyte activation in the spleen, confirming that the constructed Lister derivatives were as immunogenic as the parental virus. Thus, it appears likely that the constructed VVr/g8 virus is a safer VV vector candidate for gene therapy, immunotherapy or vaccination of humans.
Abstract 1975: Real-time FUCCI imaging demonstrates targeting dormant cancer cells
Authors: Shuya Yano, Ming Zhao, Hiroshi Tazawa, Robert M. Hoffman, Toshiyoshi Fujiwara
Journal: Cancer Research (2014)

Abstract Screening for agents that specifically kill quiescent cancer cells has not been possible due to the inability to readily identify these cells. Using cancer cells expressing a fluorescent ubiquitination-based cell cycle indicator (FUCCI), we describe here an approach to screening for agents against dormant tumor spheres consisting of cancer stem-like cells expressing CD133. In the FUCCI system, cycling cells have green fluorescent nuclei and quiescent cells contain nuclei which fluoresce red. FUCCI-expressing cancer cells in tumor spheres had predominantly red nuclei after more than 7 days without cell division. Conventional anticancer agents did not kill these quiescent cells. In contrast, the genetically-engineered oncolytic adenovirus OBP301 and Salmonella typhimurium A1-R induced quiescent cancer cells to cycle and become sensitive to DNA-damaging chemotherapy. This imaging technology provides a novel platform for visualizing trafficking candidate therapeutic agents that could decoy dormant cancer cells to cycle and become chemosensitive. Citation Format: Shuya Yano, Ming Zhao, Hiroshi Tazawa, Robert M. Hoffman, Toshiyoshi Fujiwara. Real-time FUCCI imaging demonstrates targeting dormant 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 1975. doi:10.1158/1538-7445.AM2014-1975
Crimean-Congo hemorrhagic fever in Europe: current situation calls for preparedness
Authors: H C Maltezou, L Andonova, R Andraghetti, M Bouloy, O Ergonul, F Jongejan, N Kalvatchev, S Nichol, M Niedrig, A Platonov, G Thomson, K Leitmeyer, H Zeller
Journal: Eurosurveillance (2010)

During the last decade Crimean-Congo hemorrhagic fever (CCHF) emerged and/or re-emerged in several Balkan countries, Turkey, southwestern regions of the Russian Federation, and the Ukraine, with considerable high fatality rates. Reasons for re-emergence of CCHF include climate and anthropogenic factors such as changes in land use, agricultural practices or hunting activities, movement of livestock that may influence host-tick-virus dynamics. In order to be able to design prevention and control measures targeted at the disease, mapping of endemic areas and risk assessment for CCHF in Europe should be completed. Furthermore, areas at risk for further CCHF expansion should be identified and human, vector and animal surveillance be strengthened.
Elicitation of the immune response to <i>p</i> -phenylenediamine in allergic patients: the role of dose and exposure time
Authors: C. Goebel, P.-J. Coenraads, H. Rothe, G. Kunze, M. Kock, H. Schlatter, G.F. Gerberick, B. Blömeke
Journal: British Journal of Dermatology (2010)

Usage of hair dye products containing p-phenylenediamine (PPD) is a concern for PPD-allergic individuals.The present study investigates the role of dose and exposure time on elicitation of allergic contact dermatitis under conditions of permanent hair dyeing.Elicitation responses after application of a typical hair dye product containing 2% PPD for 30 min followed by rinsing were analysed in 38 PPD-allergic individuals with a documented history of hair dye-related allergy. Skin binding experiments in vitro were performed to distinguish the dose available for elicitation from the dose applied.A positive reaction was elicited in 20 of 20 patients with grades ++ to +++ and 12 of 18 with grade + according to the classification of the International Contact Dermatitis Research Group. Under conditions of diagnostic patch testing (48 h exposure), the dose available for elicitation is more than 10-fold higher compared with the dose available for hair dyeing (30-min exposure, rinsing of product).This investigation demonstrates that under simulated hair dye use conditions the actual exposure to PPD is more than an order of magnitude lower than under diagnostic patch testing, although sufficient to elicit a clearly noticeable reaction in 84% of PPD patch test-positive individuals.
Acceptance of Rat and Mouse Lung Grafts by Radiation Chimeras&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: George W. Santos, Richard M. Garver, Leonard J. Cole
Journal: JNCI Journal of the National Cancer Institute (1960)

Rat-mouse bone marrow chimeras, i.e., lethally X-irradiated mice that had received injections of rat bone marrow, were given grafts of rat and mouse lung tissue by subcutaneous implantation at 14 to 270 days post irradiation. The lung grafts were removed 35 to 40 days after implantation, fixed in formalin, and the histologic sections examined microscopically for evidence of growth and persistence of the graft, or of rejection. In normal nonirradiated mice or in isologous chimeras (irradiated mice receiving injections of isologous bone marrow), the mouse lung grafts grew well in 73 percent of the recipients, while rat lung grafts were rejected in 100 percent of the animals. In the heterologous chimeras given grafts at 14 to 38 days post irradiation, rat lung tissue grew well in 56 percent of the animals, while mouse lung tissue grew well in only 19 percent (16 mice). In heterologous chimeras (19 mice) given grafts at 55 to 270 days post irradiation, rat lung grafts grew well in 58 percent of the mice and mouse lung grafts in 69 percent. These late chimeras appeared healthy and there was evidence of weight gain, growth of hair, and a return to normal lymphoid architecture. In one chimera, which lost its rat marrow graft at 60 days post irradiation (as evidenced by the absence of alkaline-phosphatase-positive rat granulocytes in the peripheral blood), mouse lung tissue grew well, but rat lung tissue was rejected. On the basis of the present study, in the majority of long-lived heterologous chimeras, both rat and mouse cells exist or eventually exist in varying proportions in individual mice, which are capable of some immunological response in general, but incapable of reacting specifically to host or donor-type isoantigens.
Abstract 1929: Tyrosine kinase inhibition with sorafenib but not pazopanib enriches for sarcoma cancer stem cells in diverse models of soft tissue sarcoma
Authors: Robert J. Canter, Erik Ames, Stephanie Mac, Steve K. Grossenbacher, Mingyi Chen, Joe Tellez, Arta M. Monjazeb, William J. Murphy
Journal: Cancer Research (2014)

Abstract Purpose: Cancer stem cells (CSCs) are a putative source of resistance and relapse following conventional anti-proliferative therapies. We hypothesized that anti-proliferative, but not anti-angiogenic, tyrosine kinase inhibitors would enrich for CSCs in models of soft tissue sarcoma. Experimental Design: We exposed multiple human sarcoma cell lines to sorafenib and pazopanib and assessed cell viability and expression of CSC markers. We exposed mice harboring lung/liver Ewing's sarcoma metastases to daily sorafenib and evaluated survival and CSC expression. We exposed dissociated primary sarcoma tumors to overnight sorafenib and pazopanib. We used tissue microarray (TMA) to evaluate the frequency and intensity of CSC markers in clinical sarcoma samples after neoadjuvant therapy with sorafenib. Results: Viability following sorafenib exposure in vitro ranged from 1 - 20% with a corresponding 2 - 8.2 fold increase in ALDHbright cells from baseline (P&amp;lt;0.05), while negligible effects from pazopanib were observed. In vivo, sorafenib treatment improved median survival by 10 days (P&amp;lt;0.05), but increased the population of ALDHbright cells 2.5 - 2.8 fold (P&amp;lt;0.05). Analysis of primary human sarcoma samples revealed direct cytotoxicity following exposure to sorafenib with a corresponding increase in ALDHbright cells (P&amp;lt;0.05). Again, negligible effects from pazopanib were observed. TMA analysis of clinical sarcoma specimens demonstrated significant enrichment for ALDHbright cells in the post-treatment resection specimen following neoadjuvant therapy including sorafenib (P&amp;lt;0.05). Conclusions: Sorafenib, but not pazopanib, exerts a direct anti-proliferative effect on sarcoma cells with a corresponding enrichment in sarcoma CSCs. Sustained anti-sarcoma therapeutic effects may require targeting of the CSC population in combination with cytotoxic treatments. Note: This abstract was not presented at the meeting. Citation Format: Robert J. Canter, Erik Ames, Stephanie Mac, Steve K. Grossenbacher, Mingyi Chen, Joe Tellez, Arta M. Monjazeb, William J. Murphy. Tyrosine kinase inhibition with sorafenib but not pazopanib enriches for sarcoma cancer stem cells in diverse models of soft tissue sarcoma. [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 1929. doi:10.1158/1538-7445.AM2014-1929
Abstract 12734: A New 4-group Classification of Left Ventricular Hypertrophy Based on left Ventricular Geometry Located a New High-risk Group within Eccentric Hypertrophy in Hypertensive Patients - A LIFE Study
Authors: Casper N Bang, Eva Gerdts, Gerard P Aurigemma, Kurt Boman, Markku S Nieminen, Bjorn Dahlof, Lars Kober, Kristian Wachtell, Richard B Devereux
Journal: Circulation (2012)

Background: Left ventricular hypertrophy (LVH) is traditionally classified as concentric or eccentric, based on LV relative wall thickness (RWT, wall thickness/chamber radius). We evaluated a 4-gro...
Abstract 1623: 1,4,5,8-Tetrakis-[(2-N,N-dimethylaminoethyl)amino]anthraquinone as a potential anticancer agent: its synthesis, characterization and anticancer properties
Authors: Don R. Ishmael, Orn Adelsteinsson
Journal: Cancer Research (2014)

Abstract A number of compounds based on the base compound 1,4,5,8 tetrahydroxyanthraquinone have anticancer properties. One compound of this class mitoxantrone bis-5,8 hydroxyethylaminoethylamino 1,4 dihydroxy anthraquinone has been on the market a number of years and is approved by the FDA for the treatment of: acute myelogenous leukemia, various lymphomas, breast cancer, sarcoma and the non-malignant condition multiple sclerosis. However this drug has a number of drawbacks: (1) for most cancer therapies is considered less effective than the anthracyclines, (2) although it has less cardiotoxicity than anthracyclines it does still has significant cardiotoxicity, (3) it is known to rapidly induce multi-drug resistance factors, and (4) has significant bone marrow toxicity. The class of compounds of 1,4-Bis aminoalkylamino class work against cancer cells by intercalating DNA in the major groove and inhibition of topoisomerase II enzyme. There have been a number of attempts to improve the class of drugs by adding different functional groups. However no compound of this class has exceeded the utility of mitoxantrone. Attempts to make derivatives of leuco 1,4,5,8-tetrahydroxyanthraquinone utilizing the replacement of all four hydroxyl groups for the purpose additional DNA binding or alkylation has been unsuccessful. It was discovered that 1,4,5,8-tetrachloroanthraquinone can be used as a base compound for production of compounds with potential anticancer activity. The compound 1,4,5,8-Tetrakis-[(2-N,N-dimethylaminoethyl)amino]anthraquinone was synthesized and highly purified. It was found to have greater cytotoxicity in the screening assay than mitoxantrone or adriamycin. The cytotoxicity screening was done using the BOT-2 human breast cancer cell line. This compounds may have an advantage over the Bis-derivatives with: 1) greater cytotoxicity in screening assay, 2) cheap intermediates, 3) high yields, 4) increased number of potential active groups sites and 7) removal of the para dihydroxyl groups from the cytotoxic 1,4 bisaminoalkylaminoanthraquinone. This might result in reducing the potential for cardiotoxicity. The 1,4,5,8-Tetrakis-[(2-N,N-dimethylaminoethyl)amino]anthraquinone was purified to 97.8 purity by HPLC. Initial screening in vivo mouse model B16 melanoma was done. The response was the same for mitoxantrone with considerably less toxicity. Citation Format: Don R. Ishmael, Orn Adelsteinsson. 1,4,5,8-Tetrakis-[(2-N,N-dimethylaminoethyl)amino]anthraquinone as a potential anticancer agent: its synthesis, characterization and anticancer properties. [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 1623. doi:10.1158/1538-7445.AM2014-1623
A cultural effect on brain function
Authors: E. Paulesu, E. McCrory, F. Fazio, L. Menoncello, N. Brunswick, S. F. Cappa, M. Cotelli, G. Cossu, F. Corte, M. Lorusso, S. Pesenti, A. Gallagher, D. Perani, C. Price, C. D. Frith, U. Frith
Journal: Nature Neuroscience (2000)
Involving patients in clinical research
Authors: H. Goodare, S. Lockwood
Journal: BMJ (1999)

Education and debate p 774 

Traditionally, patients have been involved in research as “subjects,” or even “objects,” but definitely not as colleagues. In 1995 the BMJ argued that “patients should help to decide which research is conducted, help to plan the research and interpret the data, and hear the results before anybody else.”1 How far have we come in the past four years in realising these hopes?

We need to recognise that patients (participants, users, consumers, what you will)2 3 have the experience and skills that complement those of researchers. They know what it feels like to suffer a particular disease and to undergo the treatments with their various side effects. They will have a good idea of which research questions are worth asking, and when a question should be framed differently.4 For instance, researchers at Mount Vernon Hospital hypothesised that moving follow up breast cancer clinics to primary care might relieve the burden on hospital outpatient clinics. After consulting women with experience of the problem, however, the protocol was redesigned to address the issue of easier access to specialists.5

Some progress has certainly been made in the …