tbuckley/cabot-search huggingface dataset:
Abstract 2972: In vitro quantification and modeling of DNA damage by histone H2A after exposure to gemcitabine and a Chk1 inhibitor
Authors: Xiaolin Kang, Erick Kindt, Shinji Yamazaki, Gabriel E. Troche, Mary E. Spilker
Journal: Cancer Research (2011)

Abstract Background: Gemcitabine is a nucleoside analog used as an anti-cancer chemotherapeutic drug. To enhance its disruption of DNA replication and repair, Chk1 inhibitors are being developed for use in combination with Gemcitabine and other cytotoxic agents. Evaluation of these therapies with mechanistic biomarkers can be an important part of the drug development process. One such biomarker is the phosphorylation of histone H2A (γH2AX), which is a DNA damage response biomarker. An ELISA based assay has been developed to quantify γH2AX. This quantitative assay provides data that is incorporated into a mathematical model relating drug exposure to DNA damage and cell viability. Experiment Design: MiaPaCa-2 cells, a human pancreatic tumor cell line, were subjected to Gemcitabine alone (0.1 to 5uM for 2 hours), a Chk1 inhibitor alone (0.1-5uM for 2 – 48 hours), or the Chk1 inhibitor in combination with 0.5 and 5uM Gemcitabine. Cellular concentrations of Gemcitabine and the Chk1 inhibitor were detected with LC/MS. DNA damage was assessed by the γH2AX ELISA at 2, 6, 24 and 48 hours after the start of incubation with drug. In addition to γH2AX, cell viability was measured by cell number at 48 hours. A mathematical model was developed to quantify the modulation of γH2AX when exposed to each drug separately and in combination. Result: Transient exposure of the cells to Gemcitabine resulted in an increase in γH2AX at later times (24 and 48 hours). The Chk1 inhibitor resulted in a dose dependent increase in γH2AX, with a greater effect being observed at later times of exposure. The combination therapy showed a greater response than Gemcitabine or Chk1 alone. However it was observed that higher doses of Gemcitabine and Chk1 in combination did not always yield the largest γH2AX response or the greatest effect on cell viability. This may be due to cellular resistance and is still being investigated. Conclusion: The ELISA based assay for γH2AX provides a quantitative assessment of the level of DNA damage. This information can then be utilized in developing mathematical models of drug action alone and in combination with other drugs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2972. doi:10.1158/1538-7445.AM2011-2972
Abstract 1031: Estrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy
Authors: Garnet L. Anderson, Rowan T. Chlebowski, Aaron K. Aragaki, Lewis Kuller, JoAnn Manson, Margery Gass, Elizabeth Bluhm, Stephanie Connelly, F Allan Hubbell, Dorothy Lane, Lisa Martin, Judith Ockene, Tom Rohan, Robert Schenken, Jean Wactawski-Wende
Journal: Cancer Research (2012)

Abstract Background: In contrast to the predominance of observational studies, in the Women's Health Initiative (WHI) trial postmenopausal women assigned to estrogen alone had a lower risk of invasive breast cancer than did those assigned placebo (LaCroix JAMA 2011;305:1305-14). Influence of estrogen use on breast cancer mortality has not been previously reported. Methods: We conducted extended follow-up of the WHI randomized, placebo-controlled trial evaluating conjugated equine estrogen (0.625 mg/d) in 10739 postmenopausal women aged 50-79 years with prior hysterectomy, to determine long term effects of estrogen use on non-invasive and invasive breast cancer incidence, invasive breast cancer characteristics and breast cancer mortality. Comprehensive breast cancer risk assessment was conducted at entry. Screening mammography and clinical breast examinations were performed at entry and yearly thereafter. Breast cancers were confirmed by medical record and pathology report review by centrally-trained physician adjudicators blinded to randomization assignment. Analyses were by intention-to-treat. The study is registered with clinical trials CT.govNCT00000611. Findings: After a mean 10.7 years of follow-up, conjugated equine estrogen use for a median of 5.9 years (range &amp;lt;1 to 10 years) was associated with lower invasive breast cancer incidence compared to placebo (151 vs. 199 breast cancers; annualized rates, 0.27% vs. 0.35%; hazard ratio [HR] 0.77; 95% confidence interval [CI], 0.62 to 0.95, P=0.02) with no difference between intervention-phase and post-intervention-phase effects (P=0.76). Sensitivity analyses adjusting for non-adherence yielded a somewhat stronger association (HR 0.68; 95% CI 0.49-0.95). Mammogram screening exams were comparable between randomization groups throughout. In the estrogen alone group fewer women died from breast cancer (6 vs. 16 deaths; annualized rates 0.009% vs. 0.024%; HR 0.37; 95% CI, 0.13 to 0.91, P=0.03) and fewer women died from all causes after a breast cancer diagnosis (30 vs. 50 deaths; annualized rate 0.046% vs. 0.076%; HR 0.62; 95% CI, 0.39 to 0.97, P=0.04).Interpretation: Use of conjugated equine estrogen for a median of 5.9 years in postmenopausal women reduced the incidence of invasive breast cancer and reduced breast cancer mortality. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1031. doi:1538-7445.AM2012-1031
F-18 FDG Positron Emission Tomographic Image of an Aortic Aneurysmal Thrombus
Authors: SUBHA RAMAN, RODOLFO NÚÑEZ, C. OLIVER WONG, HOWARD J. DWORKIN
Journal: Clinical Nuclear Medicine (2002)

RAMAN, SUBHA M.D.; NÚÑEZ, RODOLFO M.D.; OLIVER WONG, C. M.D., Ph.D.; DWORKIN, HOWARD J. M.D. Author Information
Elevated vascular endothelial growth factor (VEGF) serum levels in idiopathic myelofibrosis
Authors: F Raimondo, MP Azzaro, GA Palumbo, S Bagnato, F Stagno, GM Giustolisi, E Cacciola, G Sortino, P Guglielmo, R Giustolisi
Journal: Leukemia (2001)
The Usefulness of Tc-99m DMSA SPECT and Three-Dimensional Surface Rendering in an Asymptomatic Patient With a Single Kidney in the Pelvis
Authors: THOMAS LEITHA
Journal: Clinical Nuclear Medicine (1998)

The diagnostic problems in a clinically asymptomatic patient with a previously unknown ectopic single kidney in the pelvis and the diagnostic utility of three-dimensional surface rendering of Tc-99m DMSA SPECT for delineating ectopic functional renal parenchyma are reported. Inconclusive dynamic planar Tc-99m MAG3 renal scintigraphy was performed with the field of view centered at the upper abdomen. Twenty-four hours later, static planar Tc-99m DMSA scintigraphy 3 hours after injection delineated functional renal parenchyma only in the pelvis but did not reveal the shape of the organ. Three-dimensional surface rendering exposed a single ectopic kidney in the pelvis. This case is the first description of the advantages of three-dimensional surface rendering of Tc-99m SPECT in the diagnosis of an ectopic kidney.
Intraductal Tubular Neoplasm of the Pancreas Diagnosed by Linear Echoendoscope: Case Report and Review
Authors: Sugimori Satoshi
Journal: Endoscopy (2011)

57 years old female with epigastralgia who was found to have dilated pancreatic main duct by transabdominal ultrasound at another hospital. She was referred to our university for further evaluation. There was no abnormal findings seen in physical examination. The results of hematology, general biochemistry, and urinalysis tests were all within normal ranges except for total cholesterol of 282mg/dl. (normal:<220mg/dL) The levels of serum carbohydrate-associated antigen 19–9, s-pancreas-1, and carcinoembryonic antigen were also within normal range. Abdominal enhanced CT and MRI revealed dilated main pancreatic duct without any evidence of obvious tumor. However, EUS revealed isoechoic mass in the main pancreatic duct measuring 5.5mm in diameter at pancreatic body with following dilated duct. No invasive into pancreas parenchyma was seen. Endoscopic retrograde pancreatography demonstrated that the main pancreatic duct at pancreatic body was partially narrowed with following dilated main pancreatic duct. IDUS showed stenotic change of pancreatic duct. Several cytology and brushing cytology tests showed negative for malignancy.
AB0191 Gene and Protein Expression Profile of Peripheral Blood in Primary Sjogren's Syndrome Patients
Authors: Y. Cheng, C. Huang
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Sjogren syndrome (SS) is a chronic, multisystemic autoimmune disease characterized by lymphoplasmocytic infiltration of the salivary. Until now, its pathogenesis and diagnosis remain enigmatic. As a multisystem disease, it involves joints, hematology, lymphocyte organ, pulmonary, kidney, liver and other organs. Different organ involvements evolve from differential impression of genes and proteins. <h3>Objectives</h3> To identify gene expression profile in peripheral blood mononuclear cell (PBMC)of patients with Sjogren9s syndrome (SS) compare it to healthy volunteers, and then verify serum protein level of identified genes in peripheral blood and analyze the correlation between level of those serum protein and disease activity parameters. <h3>Methods</h3> SS patients with leucopenia and 3healthy volunteers were included.The cRNA probes prepared for total RNA were hybridized with three identical gene chips.The difference of gene expression of each patient and volunteers were compared. According to statistical analysis and pathway analysis, different expression genes were identified. Serum protein levels of two different expressed genes weredetected by enzyme-linked immunosorbent assay (ELISA) in 40 SS patients, 40 Rheumatoid arthritis (RA) patients, 24 Osteoarthritis (OA) patients and 40 healthy controls. Independent sample t-test was applied. Correlation analysis was done to investigate the relationship between two serum protein levels and disease activity parameters of SS, including number of white blood cells, organ involvement, ESSDAI score, levels of ESR, C-reactive protein (CRP), Rheumatoid Factor (RF), immunoglobin G (IgG), immunoglobin A (IgA) and immunoglobin M (IgM). <h3>Results</h3> Significant difference in the expression of 82 genes could be detected between patients and volunteers. Among these,45 were upregulated, and 37 were downregulated. Statistical difierence was calculated between patients and volunteers especially in the following two pathways: the complement and coagulation pathways (including C2, PROS1, F2R and SEPPING1) and the cytokine-cytokine receptor interaction pathway (including FASLG, MPL, CCL20 and CXCL2) (P&lt;0.01).Further study identified that CXCL2, CCL20 levels were significantly higher in SS patients than in healthy controls (P&lt;0.01). CCL20 level was significantly correlated with number of white blood cells and level of CRP, while negatively with pulmonary interstitial diseases, and positive correlation was observed between CXCL2 level andnumber of white blood cells. <h3>Conclusion</h3> This study has identified distinct gene expression profiles in PBMC from patients with SS patients with hematology involvement and healthy volunteers. Among which, CXCL2 and CCL20 play a part in the development of SS and their determination may benefit evaluation of disease activity. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5314
Tolerance and Autoimmunity
Authors: Thomas Kamradt, N. Avrion Mitchison
Journal: New England Journal of Medicine (2001)

The immunologic specificity of the antigen receptors of T cells and B cells is the result of random shuffling of the many genes that form the DNA code for the antigen-binding site of these receptors.13 Theoretically, this process could generate 109 different T-cell receptors, including some that can bind to autoantigens (these cells are often called self-reactive T cells). Tolerance is the process that eliminates or neutralizes such autoreactive cells, and a breakdown in the working of this system can cause autoimmunity.B-Cell ToleranceAutoantibodies are characteristic of many autoimmune diseases and may be the direct cause of the . . .
P351Pretreatment of mesenchymal stem cells does not enhance their recruitment to injured tissue in a model of ischemia-reperfusion injury yet abolishes their anti-inflammatory capabilities
Authors: D Kavanagh, A Boulton, M O'leary, S Suresh, PN Newsome, N Kalia
Journal: Cardiovascular Research (2014)

Purpose: Considerable interest surrounds the use of Mesenchymal Stem Cells (MSC) as therapeutics, primarily due to their low immunogenicity and ability to secrete paracrine mediators. While MSCs possess the potential to modify inflammatory injury, recruitment to injured tissues is generally poor. We investigated whether ex vivo pretreatment with cytokines or chemical factors could enhance MSC recruitment to injured tissues. We also considered whether these techniques could influence the therapeutic ability of MSCs following ischemia-reperfusion (IR) injury. Methods: Using in vitro and in vivo assays, we investigated both the adhesive and anti-inflammatory capabilities of primary murine PDGFRα+ MSCs (mMSCs) following pretreatment. For some in vitro treatments, we compared the behaviour of mMSCs to primary human MSCs (hMSCs). MSCs were treated with CXCL12, TNFα, IFNγ, H2O2 or PBS for 1 hour. Adhesion was investigated using immobilized adhesion proteins, cultured endothelium and intravital microscopy of the small intestine. To assess inflammation, neutrophil recruitment was monitored in vivo following IR injury of the small intestine (neutrophils labelled with PE-conjugated anti-Gr-1). Tissue blood flow was investigated using Laser Doppler. Results: Prior treatment of mMSCs did not enhance cell adhesion to the protein ligands ICAM-1, VCAM-1 or MAdCAM-1. Similarly, mMSC adhesion to murine colonic or cardiac endothelium was not enhanced following pretreatment. Conversely, adhesion of hMSCs to cardiac endothelium was significantly (p<0.001) enhanced following pretreatment with CXCL12 or IL-8. In an in vivo intestinal model of IR injury, mMSC recruitment was not increased in response to injury and could not be enhanced using any of the pretreatment strategies tested. Although mMSCs were not recruited to injury per se, their presence was able to significantly (p<0.05) reduce neutrophil accumulation in the jejunal villous microcirculation following IR injury. Tissue blood flow was significantly (p<0.05) enhanced in early reperfusion in mice receiving mMSCs. Pretreatment of mMSCs with TNFα abolished their ability to reduce neutrophil accumulation and improve flow. Treatment of mMSCs with TNFα resulted in significant (p<0.001) release of IL-6 (vs control). Conclusions: MSC recruitment to the IR injured murine intestine is not enhanced by the pretreatment regimes tested. Nevertheless, MSCs - when not pre-treated - were able to reduce inflammation following IR. Future studies involving MSCs (basic and clinical) should pay careful consideration to the use of pretreatment strategies.
Abstract 3655: Metronomic chemotherapy with cyclophosphamide (Cy) and celecoxib (Cel) in murine mammary adenocarcinoma tumor models: Mechanism of action
Authors: Leandro E. Mainetti, Viviana R. Rozados, Ana Rossa, Eduardo Roggero, María J. Rico, Silvia I. Gervasoni, Ricardo Giordano, O. Graciela Scharovsky
Journal: Cancer Research (2010)

Abstract Metronomic chemotherapy (MCT) refers to the chronic, equally spaced, delivery of low doses of different chemotherapeutic drugs, without extended interruptions. CY, administered in low dose, is able to modulate the immune response. It can also reduce tumor angiogenesis, like the COX-2 inhibitor CEL does. We have already demonstrated that the administration, as an intervention strategy, of metronomic CY + CEL in M-406 and M-234p mammary adenocarcinomas-bearing mice inhibited tumor growth, increasing the survival rate. Our present aim was to study the mechanism by which that therapeutic effect was achieved. CBi and Balb/c inbred mice were s.c. challenged on day 0 with M-406 or M-234p mammary tumors, respectively, and treated from day 8 (M-406) and 5 (M-234p) on with: I) no further treatment (controls); II) CY in the drinking water (25-30 mg/kg body weight/day); III) CEL (30 mg/kg p.o.), five times/week; IV) Treated as II + III. Blood samples were taken on days 0, 20 (M-406) and 30 (M-324p) to evaluate VEGF serum level determined by ELISA and the % of circulating regulatory T cells (Tregs) by flow cytometry. The same tumor challenges and therapeutic schedules were performed in nude mice. Tumors were excised on days 20 and 30 for M-406 and M-234p, respectively, fixed and paraffin embedded for detection by immunohistochemistry of CD34 and Ki67 molecules. The VEGF serum level of M-406-bearing control animals (group I) was, on day 20, significantly higher than that measured on day 0 (p&amp;lt;0,001), while groups II, III y IV showed, on day 20, lower values than group I (p&amp;lt;0.01) in the same day, and similar than those on day 0. The % of CD4+ CD25+ Foxp3+ Treg cells in serum showed no differences between days 0 and 20 in all the experimental groups. The antitumoral effect of MCT was the same in euthymic and athymic mice. Immunohistochemistry for CD34 showed slight differences between control and treated animals that were not significant. Also, the staining for the proliferation marker Ki67 did not evinced differences among the experimental groups. The results obtained with M-234p tumor model were similar to those of M-406. In conclusion, the antitumor effect of MCT with CY plus CEL in mammary tumor models would be achieved, at least in part, by the inhibition of tumor angiogenesis, without modulation of the antitumor immune response. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3655.
A Critical Appraisal of Pinhole Scintigraphy of the Ankle and Foot
Authors: Clayton Frater, Louise Emmett, William van Gaal, Jai Sungaran, Delan Devakumar, Hans Van der Wall
Journal: Clinical Nuclear Medicine (2002)

Background Scintigraphy is an established imaging technique for injuries of the ankle and foot that are not apparent on plain radiographs. The scintigraphic technique has varied, with planar and pinhole images being used. Materials and Methods The incremental value of pinhole scintigraphy over planar imaging was studied in 16 patients with established diagnoses. Inter-reporter reproducibility was also measured. Results Pinhole scintigraphy improved the diagnostic specificity in nearly one half of the patients (48%). It did not contribute substantial information in 46% and led to confusion in the diagnosis of one patient. Inter-reporter agreement was good, with a kappa value of 0.78. Diagnoses varied from fractures of the talar dome to avulsion fractures of the malleoli and impingement syndromes. Conclusions Pinhole images add a significant incremental value to planar scintigraphy of the foot and ankle. Although this had been perceived intuitively in the past, it has not been critically evaluated. The technique has good inter-reporter agreement.
P53 * THE METABOLIC AUTOPHAGY PATHWAY REGULATES THE RESPONSE TO TEMOZOLOMIDE IN GLIOBLASTOMA MULTIFORME-INITIATING STEM CELLS
Authors: A. Swampillai, D. Brierley, S. Galavotti, A. Lampada, M. Shaked-Rabi, A. McEvoy, S. Brandner, S.-A. Martin, S. Short, P. Salomoni
Journal: Neuro-Oncology (2014)

INTRODUCTION: Glioblastoma multiforme (GBM) remains a challenge for clinicians due to resistance to conventional treatment with the DNA-damaging agent temozolomide (TMZ) and radiation. Improving outcomes has become imperative and there is a growing interest in targeting cancer cell metabolism. Based on work from our group and others, the metabolic autophagy pathway has emerged as a promising therapeutic target. There are a large number of clinical trials based on the autophagy inhibitor hydroxychloroquine (HCQ) and chloroquine (CQ), including a multi-centre Phase II study set up by our institution. While in established GBM cell lines autophagy acts as a pro-survival signal upon radiation, its role in GBM-initiating neural stem cells (GNS) in response to genotoxic stress is unknown.The objective of the present work is to investigate the role of autophagy in regulation of TMZ sensitivity in GNS. METHOD: We inhibited autophagy by pharmacological means and by stable knockdown of the essential autophagy gene ATG7. To study the response to TMZ, we have used viability assays, growth curves and western blots. RESULTS: Our findings show that both genetic and pharmacological inhibition of autophagy sensitises MGMT+ GNS cells to TMZ. In contrast, autophagy suppression does not affect the response to TMZ in MGMT- GNS cells, as well as in cells that have developed resistance via loss of hMSH6. Notably, autophagy inhibition results in downregulation of MGMT via a posttranscriptional mechanism. CONCLUSION: Modulation of MGMT is clinically relevant and this study has the potential to increase our understanding of mechanisms regulating sensitivity to DNA damaging agents in GBM.
Exhibition: Medicine without doctors
Authors: Adrian Gonzalez
Journal: BMJ (2003)

The current obsession with health foods, vitamins, exercise, and spiritual relief from stress may come in for some stick from the scientific community, but how new is it? People have always faced acute and chronic illnesses, and they have not always left everything to doctors.​doctors.




Figure 1



Amulets were carried as personal protection against plague




This exhibition, drawing on the collections of the Wellcome Foundation and the Science Museum, explores contemporary and historical attitudes to health and illness, and how humans have dealt with disease. There is evidence here of all kinds of treatments and amulets that have been used throughout history to cure plague or to lose weight. Ingeniously divided into six parts, this exhibition is a combination of science, empirical treatments, and faith.

At the entrance visitors will find a big pink corridor, with speakers emitting the sounds of various alarm clocks; stand there for more than a couple of seconds and the noise will drive you crazy. At the end of the corridor is the main exhibition room; it is all painted white, which creates the impression of a strange minimalist hospital room.

Within this are six smaller sections, such as the evacuation and retention room, where visitors can find a range of objects all relating to “evacuating” activities. On display are a potty used in the 1800s and a new diagnostic toilet with an internet connection that can help people identify disease through “sample analysis” and then communicate directly with doctors if they suspect any problems.

The airs, waters, and places room features the ancient diagnosis of nostalgia, which could be cured only by returning home. There are also illustrations showing how people used to cure neurasthenia through hydrotherapy.

The passions of the soul room explores the relationship between health and religion. Among the objects on display here are votive offerings aimed at curing disease. The three other rooms in the exhibition are devoted to food and drink, sleep and wakefulness, and motion and rest. In total there are more than 100 objects on show plus the works of 12 contemporary artists.