tbuckley/cabot-search huggingface dataset:
Abstract 1500: Modulation of recombinant vaccinia virus vector immunogenicity
Authors: Nermin Raafat, Chantal Mengus, Michael Heberer, Giulio C. Spagnoli, Paul Zajac
Journal: Cancer Research (2010)

Abstract Recombinant poxviruses expressing tumor associated antigens (TAAs) are evaluated since 20 years as immunogenic vaccine vector in clinical trials. Possible limitation to recombinant viral vector is due to either prior systemic immunity to poxviruses or immunodominance of viral antigens which may reduce the induction of immune response against weaker tumor antigens. To address this issue, we developed a recombinant Vaccinia virus expressing HSV type I protein ICP47. This protein down-regulates MHC class-I antigen presentation by blocking the transporter associated with antigen processing (TAP), which translocates peptides, generated by proteasomal protein degradation, into the endoplasmic reticulum for loading onto MHC class I molecule. Herpes simplex virus (HSV) US12 gene, coding for infected cell protein 47 (ICP47) was introduced into wild type vaccinia virus and into a r.VV expressing MART-1/Melan-A27–35 HLA-A201 endoplasmic reticulum (ER)-targeted epitope. Following infection with non-replicating recombinant virus, effect of ICP47 expression on cell surface MHC-class-I, MHC class-II and co-stimulatory molecules was characterized by antibody staining and FACS analysis. Human T-lymphocytes were stimulated in vitro with autologous CD14+ cells infected with r.VV-US12, r.VV-Mart-US12 or control virus. Responsiveness of specific CD8+ and CD4+ to viral proteins and recombinant epitopes were monitored by MHC-multimer staining and interferon gamma (IFNg) expression analysis. Cells infected with HSV-US12-r.VV, demonstrated a decreased ability of presenting MHC class-I antigens to CD8+ T cells whereas MHC-class-II restricted presentation to CD4+ T cells remained unaffected. Co-expression of ER-Melan-A/Mart-126–35 appeared to partially compensate for the ICP47 related surface MHC class-I molecule down-regulation and preserve a strong capacity to induce CTL response against the TAA derived peptide. Thus, viral vectors expressing ICP47 confirmed a diminished TAP-dependant processing of endogenous class-I restricted epitopes while the immunogenic potential of recombinant epitopes directly targeted to the ER was enhanced. Such reagents could become of high relevance especially in multiple-boost vaccine protocol required in cancer immunotherapy. 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 1500.
La Crosse Encephalitis in Children
Authors: James E. McJunkin, Emily C. de los Reyes, Jose E. Irazuzta, Manuel J. Caceres, Raheel R. Khan, Linda L. Minnich, Kai D. Fu, Gretchen D. Lovett, Theodore Tsai, Ann Thompson
Journal: New England Journal of Medicine (2001)

La Crosse encephalitis is a mosquito-borne disease that can be mistaken for herpes simplex encephalitis. It has been reported in 28 states but may be underrecognized.We investigated the manifestations and clinical course of La Crosse encephalitis in 127 patients hospitalized from 1987 through 1996. The diagnosis was established by serologic testing for IgM and IgG antibodies to La Crosse virus. Data were collected by chart review.Most of the patients were school-aged children (mean [+/-SD] age, 7.8+/-3.5 years; range, 0.5 to 15.0). Symptoms included headache, fever, and vomiting (each in 70 percent or more of the patients), seizures (in 46 percent), and disorientation (in 42 percent). Thirteen percent had aseptic meningitis. Hyponatremia developed in 21 percent, and there were signs of increased intracranial pressure in 13 percent. Six patients, including three with cerebral herniation, underwent intracranial-pressure monitoring. The 13 patients (11 percent) whose condition deteriorated in the hospital had decreases in serum sodium levels (P=0.007), and increases in body temperature (P=0.003) at the time of deterioration. At admission, these patients more often had a history of vomiting (P=0.047) and a score of 12 or lower on the Glasgow Coma Scale (P=0.02) than the others; a trend toward a greater prevalence of seizures at admission was also evident in this group (P=0.07). All the patients survived, but 15 of them (12 percent) had neurologic deficits at discharge. Follow-up assessments, performed in 28 children, suggested an increase in cognitive and behavioral deficits 10 to 18 months after the episode of encephalitis.La Crosse virus infection should be considered in children who present with aseptic meningitis or encephalitis. Hyponatremia and increasing body temperature may be related to clinical deterioration.
Circulating Erythroid Progenitors in the Anemia of Prematurity
Authors: Kevin M. Shannon, Gordon S. Naylor, Joseph C. Torkildson, Gisela K. Clemons, Vann Schaffner, Steven L. Goldman, Kathleen Lewis, Paulette Bryant, Roderic Phibbs
Journal: New England Journal of Medicine (1987)

We studied erythropoiesis in infants with the anemia of prematurity by counting the number of colonies derived from erythroid burst-forming units (BFU-E) in the blood of 11 premature infants before they received transfusions. Colony growth in blood from the infants was compared with growth in blood from adults and umbilical-cord blood from term infants, in the presence of erythropoietin, 0 to 2000 mU per milliliter. Addition of increasing concentrations of erythropoietin resulted in a stepwise increase in the number of colonies derived from BFU-E (P<0.0005) of all three groups of subjects. Cultures stimulated with 2000 mU of erythropoietin yielded 28.1±7.6, 88.0±19.4, and 121.0±22.5 bursts (mean±SE) per 105 cells plated in blood from adults, blood from premature infants, and cord blood, respectively. Although more BFU-E–derived colonies appeared when 200 or 2000 mU were present per milliliter in cultures of the infants' blood and cord blood, the intrinsic responsiveness of BFU-E to erythropoietin was similar in all groups. Although the mean hematocrit was 26 percent, mean serum erythropoietin concentrations (±SD) in the infants (20.7± 10.0 mU per milliliter) were not significantly different from those in the adult controls (24.0±6.5). We conclude that progenitor cells committed to erythroid differentiation are present during the anemia of prematurity, and that the intrinsic responsiveness of the circulating BFU-E pool to erythropoietin is normal. These results implicate inadequate production of erythropoietin as the cause of the anemia of prematurity and suggest that recombinant erythropoietin might provide a therapeutic alternative to transfusion for symptomatic babies with this condition. (N Engl J Med 1987; 317:728–33.)
Grade 3 Status Dominates Prognosis in Breast Cancer.
Authors: S. Oliveros, K. Unger, M. Morishita, C. Davies, M. Gudi, G. Thomas, R. Leonard
Journal: Cancer Research (2009)

Abstract Background: Histological grading (HG) is probably the most important clinico-pathological parameter that will provide information about tumour intrinsic characteristics and aggressiveness. HG is included in prognostic guidelines for treatment decision making such as St Gallen, Nottingham Prognostic Index and Adjuvant!Online. Grade 3 (G3) Breast cancer (BC) is associated with poor prognosis in terms of survival and recurrence. G3 BC reflects independent biological entities rather than being the end of the spectrum of cancer progression. Our aim is to establish the clinical relevance of HG as prognostic factor in a specific cohort of BC patients and define its relation with survival and recurrence endpoints.Method: This is a retrospective cohort analysis from 1489 operable Breast Cancer patients attending the Oncology Service at Singleton Hospital, Wales, UK between 1996 and 2002.HG was recorded for 1339 cases and outcome data were available on 1213 cases. Correlation of clinical variables with Overall Survival (OS), Distant Disease Free Survival (DDFS) and Disease Free Survival (DFS) was performed using Cox regression model.Results:The median follow-up for the cohort was 5.43 years (range 0.09 to 10.14 years) Patients were characterised according to age, HG, tumour size (TNM-T), nodal status, ER status and systemic treatment received (polychemotherapy/tamoxifen). Independent Cox regression models for each endpoint were developed based on univariate analyses. Multivariate analysis results are presented in Figure 1.Subgroup analysis of G3 cases showed a younger population: median age G3 59.4y vs G1/G2 62.9 y p:&amp;lt; 0.001); 47.5% of G3 cases were ER positive against 94.5% of Grade 1/2 (p &amp;lt; 0.001). Patients with G3 tumours died more rapidly from all causes (median time to death 2.22 vs 3.42 y, p &amp;lt;0.001) and from BC (median time to death from BC 2.22 y vs 3.82 y in G1/G2, p &amp;lt;0.001) than other HG. Similarly, G3 also relapsed quicker both distantly, (median time 1.64 vs 2.54 y G1/G2 (p&amp;lt;0.04) and locally, median time to relapse 1.6 vs 2.35 y for G1/G2 (p&amp;lt;0.036). There was also a significant association between grade and tumour size (median G1/G2 1.7cm vs G3 2.2cm(p&amp;lt; 0.001); and nodal involvement and tumour size, median 1.5cm N-ve, 2.2 cm N+ve (p&amp;lt; 0.001).Conclusion: Patients with G3 tumours tended to be younger, had a more advanced TNM staging at diagnosis and relapsed and died more rapidly than other histological grades. In our cohort, G3 tumours were adversely associated with OS, DDFS and DFS with a stronger association with these endpoints than node positivity. It is perhaps time to reconsider the HG as a prognostic factor as important as nodal status for the selection of adjuvant chemotherapy regimens. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6005.
Case 32-2011
Authors: Uzma Shah, Anuradha S. Shenoy-Bhangle
Journal: New England Journal of Medicine (2011)

A 19-year-old man was admitted to this hospital because of recurrent pancreatitis, associated with alcohol use, beginning 6 months earlier. On examination, he was obese and had upper abdominal tenderness. Imaging studies showed normal pancreatobiliary anatomy.
Percutaneous Injuries before and after the Needlestick Safety and Prevention Act
Authors: Elayne K. Phillips, Mark R. Conaway, Janine C. Jagger
Journal: New England Journal of Medicine (2012)

According to this analysis of needlestick injuries in a sample of U.S. hospitals before and after passage of the NSPA in 2000, the number of percutaneous injuries per 100 full-time hospital employees declined after enactment of the legislation.
Abstract P4-02-05: A novel 64Cu-liposomal PET agent (MM-DX-929) predicts response to liposomal chemotherapeutics in preclinical breast cancer models
Authors: H Lee, J Zheng, D Gaddy, D Kirpotin, M Dunne, D Drummond, C Allen, D Jaffray, B Hendriks, T Wickham
Journal: Cancer Research (2012)

Abstract Background: Liposomal anthracyclines (such as pegylated liposomal doxorubicin (PLD) or HER2-targeted liposomal doxorubicin (MM-302)) are being used and/or evaluated for the clinical management of breast cancer, but responses vary from patient to patient. It is hypothesized that variability in the deposition of liposomal therapeutics within tumors leads to differences in drug exposure, thereby directly influencing tumor response. We have developed MM-DX-929, a novel 64Cu-liposomal PET imaging agent, as a clinically-implementable tool to investigate whether image-based quantification of liposome deposition in tumors can predict treatment response to liposomal chemotherapeutics, including PLD, MM-302 and/or liposomal irinotecan (MM-398). Objectives: Our primary objective is to demonstrate that the extent of tumor uptake of MM-DX-929 is predictive of tumor response to MM-302 in preclinical breast cancer xenograft models. A secondary objective is to enable clinical translation of MM-DX-929 to enable incorporation into existing therapeutic trials. Methods: Mice bearing BT474-M3 mammary and subcutaneous tumors were injected intravenously with MM-DX-929 prior to dosing with MM-302. PET/CT imaging was performed at 16h post MM-DX-929 injection, and tumor uptake was determined. Response to treatment was quantified as tumor volume changes measured over a 2-month period by MRI. Results: Tumor deposition of MM-DX-929 administration correlated well with treatment response to MM-302 (Spearman correlation coefficient of −0.891 and a p-value of 0.0004). MM-DX-929 accumulation in tumors prior to the start of the MM-302 treatment successfully predicted improved tumor growth inhibition following MM-302 treatment. Conclusion: These findings support trials of MM-DX-929 as a predictive imaging agent to select patients who are most likely to respond to liposomal therapies. The clinical development of MM-DX-929 for identification of breast cancer patients likely to respond to liposomal therapeutics is currently being pursued. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P4-02-05.
FFR-Guided PCI — FAME May Not Be So Fleeting after All
Authors: Jeffrey J. Rade
Journal: New England Journal of Medicine (2014)

Treatment strategies for patients with stable coronary artery disease are driven by the principles of reducing symptoms of coronary insufficiency, preventing myocardial infarction, and prolonging survival. Although percutaneous coronary intervention (PCI) plays a primary role in treating acute coronary syndromes, current guidelines relegate it largely to a secondary role in treating stable coronary disease.1,2 These recommendations are derived from studies, most notably the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, which showed that angiography-guided PCI plus medical therapy, though effective at reducing symptoms, was no better at preventing death or myocardial infarction than medical therapy alone. . . .
CARACTERIZACIÓN CLÍNICO-PATOLÓGICA DEL SÍNDROME DE POLIPOSIS SERRADA
Authors: S Carballal Ramil, M López-Ceron, L Moreira, ML Leoz, T Ocaña, M Cuatrecasas, D Rodriguez-Alcalde, A Castells, M Pellisé, F Balaguer
Journal: Endoscopy (2013)

Introducción: el síndrome de poliposis serrada (SPS) se asocia a una probabilidad aumentada de desarrollar càncer colorrectal (CCR). Sus características clínico-patológicas y el riesgo de CCR en los individuos y sus familiares no están bien establecidas. Objetivo: describir las características clínico-patológicas del SPS en una serie amplia de pacientes. Material y Método: anàlisis retrospectivo de una cohorte de 67 pacientes con SPS evaluados en el Hospital Clínic de Barcelona entre los años 2005 y 2013. Resultados: la edad media al diagnóstico fue de 55 años y 41(61,2%) eran varones. El 67% (n = 45) eran fumadores. Veintisiete pacientes (40,3%) fueron derivados desde el programa de cribado poblacional de CCR. Se detectaron 1781 pólipos serrados (PS) y 298 adenomas en 268 colonoscopias y 23 piezas quirúrgicas (tiempo medio de seguimiento: 18 meses). El 76% tenía algún adenoma. Los PS se clasificaron en: 1048 pólipos hiperplásicos (PH), 724 adenomas serrados sésiles (ASS) y 9 adenomas serrados tradicionales. Un 4% de PS tenía displasia asociada. En 29 (43%) pacientes se utilizó cromoendoscopia, cuyo uso se asoció a una mayor detección de PS proximales y planos que la luz blanca (19,3 vs. 11,6; p = 0,05 y 11,2 vs. 3,5; p = 0.02, respectivamente). Trece individuos (19,4%) desarrollaron14 CCR (5 antes del diagnóstico de SPS, 5 simultáneamente y 3 durante el seguimiento). El desarrollo de CCR se asoció al número de ASS proximales (14 vs. 9,7; p = 0.03) y el sexo femenino (69,2% vs. 31,5%; p = 0,02). Diecisiete (25,4%) individuos requirieron cirugía por falta de control endoscópico. Conclusiones: El SPS confiere un alto riesgo de desarrollar CCR y adenomas. Los programas de cribado poblacional de CCR son clave para identificar pacientes con SPS. En nuestra población el sexo femenino y el número de ASS proximales se asociaron a mayor riesgo de CCR. La cromoendoscopia mejora la detección de PS planos y proximales.
A Stinging Sensation
Authors: Kathleen Lee-Sarwar, Anand Vaidya, Min Shi, Cem Akin
Journal: New England Journal of Medicine (2015)

Approximately 10 minutes after being stung on the right lower leg by a yellow jacket (a type of wasp), a 45-year-old man began to feel light-headed and nauseated. He called emergency medical services, and paramedics arrived 10 minutes later. They found him to be alert but anxious, with scattered areas of erythema on his trunk and a small, localized area of tenderness, swelling, and erythema . . .
Abstract 4069: Determination of single cell surface protein expression using a tagless microfluidic method
Authors: Sri HariKrishna Vellanki, Robin Smith, Rajan Kumar, Robert Wieder
Journal: Cancer Research (2012)

Abstract Tumors are often inaccessible to biopsy and fine needle aspirates are often the only source of cellular material from tumors either at diagnosis or during therapy for determination of pharmacodynamic response. The few cells that needle aspirates yield are not sufficient for more than visual diagnostic determination of malignancy or potential tumor category. Most processing would result in the loss of these cells and is impractical. A need exists for a different diagnostic tool that can obtain biologically relevant information from cells when only few are available without the need for processing them. We describe a method to detect the expression of a surface protein in single cells without prior labeling or manipulation using a microfluidic device. When the protein is expressed, it undergoes transient bond formation with a ligand immobilized on a patch as the cell is pumped through a microfluidic device, resulting in a specific decrease in the cell's velocity. We sterile sorted LM2 cells, a subline of MDA-MB-231 human breast cancer cells, with a unique lung metastatic capability, into fractions expressing none (P1), medium (P2) and high levels (P3) of interleukin13α2 receptor (IL13Rα2). We used variable chamber heights (25, 50, 75 μm), width 7 mM and 1%, 1.5%, 2.5% glycerol in buffer with variable flow rates. We were able to get specific flow retardation with reduction in mean velocity 15.1 % with shear rate 62.86 (s−1) and shear stress 0.63 (dynes/cm2) in the fraction expressing high levels (P3) of IL13Rα2 receptor compared to controls LM2 (P1), MDA-MB-231, MCF-7 cells. The detection of cells with high expression of the protein (P3) was 100% sensitive and 100% specific. Later we asked the following questions: can cells be reanalyzed after pumping through microfluidic device, can we indentify IL13Rα2 positive cells in mixture and whether specificity of flow retardation is due to antigen and antibody binding. The method is non-destructive and P3 cells can be collected for reanalysis and we got reduction in mean velocities in first and second run 9.7% and 10.0%. The system could identify P3 positive cells with mean velocity reduction 5.5% when mixed with MDA-MB-231 cells in 1:1 ratio and the interaction between the antigen/antibody is highly specific as the mean velocity reduction in P3 cells is 0.2%. Further needle aspirates from mice xenograft were able to detect cells expressing IL13Rα2 receptor. This method will have a potential impact in analyzing cancer cells when only few are available, such as the case with needle aspirates, when labeling and manipulation results in cell loss. 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 4069. doi:1538-7445.AM2012-4069
Abstract 5121: A targeted approach to identify activators of class IA phosphoinositide-3-kinase in cancers using tandem mass spectrometry
Authors: John M. Asara, Lewis C. Cantley, Jeffrey A. Engelman
Journal: Cancer Research (2011)

Abstract A majority of human cancers exhibit aberrant activation of the phosphoinositide 3-Kinase (PI3K) pathway. In many cases this activation is due to mutations or amplifications in upstream activators of PI3K resulting in activation by direct binding of phosphotyrosine proteins (e.g., receptor tyrosine kinases (RTK) or adaptors such as IRS-1/2 or Gab1/2) to the p85 regulatory subunit of PI3K. To date, experiments to identify the mechanisms of PI3K activation in cancer have remained difficult and cumbersome. Since inhibitors of many of these RTKs are either already approved or in clinical trials, identification of the major upstream activators of PI3K in a given tumor could suggest the appropriate therapeutic intervention. Here we present a quantitative mass spectrometry approach (targeted ion MS/MS – TIMM) for identifying the upstream activators of PI3K in cancer cell lines grown on plastic as well as in tumor Xenografts. Importantly, we show that in a series of non small cell lung carcinoma cell lines, it is possible to predict the appropriate drug for treating the cells based on the upstream activator of PI3K as revealed by TIMM. Specifically, we identified how PI3K is activated in MET amplified, EGFR and EML4-ALK driven non-small cell lung cancers (NSCLCs) both in vitro and in vivo, and were successful in identifying the optimal RTK inhibitor treatment for the H1703 NSCLC cell line. Additionally, this technology revealed that TORC1 inhibition leads to activation of PI3K via IRS-2, not IRS-1 in KRAS mutant cell lines. 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 5121. doi:10.1158/1538-7445.AM2011-5121
SAT0137 Treatment with certolizumab pegol in RA – data from the national registry artis (antirheumatic therapies in sweden)
Authors: K. Chatzidionysiou, R. van Vollenhoven
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Certolizumab pegol (Cimzia) is a pegylated TNF inhibitor approved for the treatment of RA. Its efficacy and safety are well established from clinical trials. <h3>Objectives</h3> To evaluate and describe the efficacy and drug survival of certolizumab pegol in real-life patients. <h3>Methods</h3> Data from the national registry ARTIS were used for this analysis. Patients with RA, who started treatment with certolizumab pegol were identified. Clinical response was assessed by DAS28 and HAQ improvement as well as EULAR response criteria. <h3>Results</h3> During the period from Nov 1st, 2009 until September 29th 2011, a total of 196 patients with a diagnosis of RA started treatment with certolizumab pegol. The mean (SD) age and disease duration of the patients was 56.8 (12.7) and 11.9 (10.3), respectively. 80.1% of patients were RF positive, 72.4% were female and 61.7% had concomitant DMARDs. All patients had failed conventional DMARDs and the majority had failed at least one prior biologic. Significant reductions (mean±SD) of DAS28 from baseline (4.9±1.3, N=166) to 3 months (3.8±1.5, N=84) and 6 months (3.5±1.5, N=58) were observed (p&lt;0.0001). Similarly HAQ was reduced from 1.2±0.7 at baseline, to 1.0±0.7 at 3 and remained stable at 6 months (p=0.002). At 3 months the percentages of EULAR Good/Moderate/No responders were 23.8/61.9/14.3% [N patients=84], and at 6 months 25.9/55.2/19% [N patients=58]. 27.4% and 31% of patients achieved DAS28&lt;2.6 at 3 and 6 months, respectively. During the follow-up period 32 patients (16.3%) discontinued treatment with certolizumab pegol: 15 because of lack of efficacy, 7 because of intolerance and 10 for unknown reasons. The mean (SD) time to discontinuation was 3.2 (1.8) months. 20 patients discontinued certolizumab pegol during the first 3 months. In figure 1 the drug survival of certolizumab pegol is shown. <h3>Conclusions</h3> In this observational cohort of RA patients with long-standing and refractory disease who were treated with certolizumab pegol, 80% achieved a EULAR Good/Moderate response, and about one fourth achieved a EULAR Good response and/or a DAS28&lt;2.6. <h3>Disclosure of Interest</h3> None Declared