tbuckley/cabot-search huggingface dataset:
Abstract 755: Dendritic-cell vaccine: Cross-presentation of carcinoembryonic antigen (CEA) by dendritic cells (DCs) through a fusion protein targeting CD74 on DCs
Authors: Xiaochuan Chen, Chien-Hsing Chang, Rhona Stein, David M. Goldenberg
Journal: Cancer Research (2011)

Abstract Milatuzumab (hLL1, Immunomedics, Inc.) is a humanized anti-CD74 monoclonal IgG1 antibody (mAb) currently in phase I-II clinical trials as a therapeutic mAb for CD74-expressing non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma. Since CD74 is also expressed by normal antigen-presenting cells (APCs), including DCs, we investigated the potential application of the Fab fragment of hLL1 as a novel targeting vector in a cancer vaccine. Methods: A fusion protein, hLL1-Fab-A3B3, was constructed by fusing the Fab fragment of milatuzumab to the A3B3 domain of CEA. The binding profiles and cytotoxic potenial of hLL1-Fab-A3B3 on APC subsets in human peripheral blood mononuclear cells (PBMCs) were assessed by flow cytometry; the impact of hLL1-Fab-A3B3 on APC function was assessed by allogeneic mixed leukocyte reaction (MLR) through CFSE-based cell proliferation assay. The cross-presentation of CEA by DCs was evaluated by three rounds of weekly stimulation of autologous T cells with DCs loaded with hLL1-Fab-A3B3 or CEA protein, followed by measuring CEA-specific CD8+ T cells with HLA-A*0201-restricted CAP-1 pentamer (YLSGANLNL). Results: Both bivalent milatuzumab and monvalent hLL1-Fab-A3B3 bound efficiently to human APC subsets, which include BDCA-1+ myeloid DCs type 1 (mDC1), BDCA-2+ plasmacytoid DCs (pDCs), BDCA-3+ myeloid DCs type 2 (mDC2), B lymphocytes, and monocytes, but neither of the two bound to T cells. While milatuzumab selectively reduced mDC1 (by 60.8%, P=0.003, n=6 donors) and mDC2 (by 53.8%, P=0.0026, n=7 donors) in PBMCs, presumably mediated by the presence of Fc, or a necessity for divalent milatuzumab binding, hLL1-Fab-A3B3 did not have this effect, nor did it affect the viability of T cells and other APC subsets (pDCs, monocytes, and B cells). The allogeneic MLR was significantly inhibited by milatuzumab (P&amp;lt;0.0001), but not by hLL1-Fab-A3B3 treatment (P=0.6644). After three rounds of weekly stimulation of autologous T cells, DCs loaded with hLL1-Fab-A3B3 were more efficient in inducing CEA-specific CD8+ T cells than DCs loaded with CEA, suggesting that the hLL1-Fab enhances the cross-presentation of CEA by DCs. Conclusion: hLL1-Fab is a promising, novel targeting antibody for use as a cancer vaccine, because it enhances the cross-presentation of antigens without significant cytotoxicity and functional alteration on APCs. 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 755. doi:10.1158/1538-7445.AM2011-755
PMO-066 Salvage of occluded central venous catheters in long term parenteral nutrition patients: techniques &amp; outcomes: Abstract PMO-066 table 1
Authors: G A D Major, M Small, S M Gabe
Journal: Gut (2012)

<h3>Introduction</h3> Central venous catheter (CVC) occlusion is a recognised complication of parenteral nutrition (PN). Various techniques are advocated to salvage the CVC but forcing debris from fibrin or precipitate into the bloodstream risks causing catheter-related bloodstream infection (CRBSI) or embolism. We decided to assess the efficacy of simple physical techniques to salvage an occluded CVC, and the rate of complications described. <h3>Methods</h3> All CVC occlusions between January 2010 and December 2011 were reviewed. Occlusions were “total”, when the CVC could not be flushed, or “partial”, when there was resistance to flushing. The cause of occlusion was recorded together with the time from symptom onset to attempted salvage, age of the CVC, techniques and instillations used to unblock the CVC, and outcomes. Confirmed cases of CRBSI occurring within 30 days of CVC salvage were recorded. Techniques included: manipulation of the external segment of the CVC to disrupt visible material (M); saline flush of the CVC with a gentle, pulsing action using a 2.5 ml Luer lock syringe for 20–60 min (SF); instillation of alcohol to dissolve lipid (A); pulsed flushing of urokinase without instillation (U); physical clearing out of the CVC hub with a 21G needle to remove any obstructing material (HC). <h3>Results</h3> 38 occlusions occurred in 23 patients giving an occlusion rate of 10.9% (0.25 occlusions/1000 catheter days): 11 partial occlusions in five patients and 27 total occlusions in 19 patients. See Abstract PMO-066 table 1 below: The rate of CRBSI in this group was 0.02 CRBSI/1000 catheter days in the 2-year period assessed. This compares with a rate in patients not suffering occlusions of 0.91 CRBSI/1000 catheter days. <h3>Conclusion</h3> CVC salvage is often possible with line manipulation and persistent pulsatile flushing. Hub clearout with a needle is also safe and effective. Alcohol and urokinase have an occasional role but are often not required and may not work without additional measures. Post-salvage complications are rare. The apparent negative association between occlusion and infection runs contrary to the belief that infection and occlusion are linked, and warrants further study. <h3>Competing interests</h3> None declared.
Drawing Medical Students into Research: Hughes Program Expands
Authors: C. Vanchieri
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Drawing Medical Students into Research: Hughes Program Expands Get access Cori Vanchieri Cori Vanchieri Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 17, 2 November 1988, Pages 1358–1360, https://doi.org/10.1093/jnci/80.17.1358 Published: 02 November 1988
UTILIDAD DE LA ECOENDOSCOPIA EN EL DIAGNÓSTICO DE PANCREATITIS AUTOINMUNE EN NUESTRO MEDIO
Authors: C Consiglieri Alvarado, JB Gornals Soler, C Loras Alastruey, C Pons Vilardell, I Catala Costa, X Sanjuan Garriga, N Baixeras Gonzalez, J Busquets Barenys, N Pelaez Serra, R Llatjos Sanuy, M Varas Lorenzo
Journal: Endoscopy (2013)

Introducción: la pancreatitis autoinmune (PAI) es una patología infrecuente en nuestro medio, en la que puede estar indicada la práctica de una ecoendoscopia. Objetivo: describir nuestra experiencia sobre el papel de la ecoendoscopia en el manejo diagnóstico de la PAI. Material y Método: revisión retrospectiva de pacientes con sospecha inicial de PAI por pruebas de imagen y datos clínicos, que se les realizó USE sin punción (n = 3) y con punción (n = 12) (22 G, 19G, Quick-Core®) durante el período 2008 – 2013 por un mismo grupo de trabajo, en 3 centros hospitalarios. Variables analizadas: edad, sexo, indicación clínica, signos de imagen USE, hallazgos citohistológicos, evolución clínica posterior. Resultados: se revisaron 15 pacientes (11 hombres, 42,5 ± 3,8 años). La presentación clínica fue: ictericia obstructiva (n = 7), pancreatitis aguda (n = 7), fibrosis peritoneal (n = 1). Signos patológicos por imagen USE descritos: aumento difuso del páncreas (n = 15), patrón parenquimatoso atigrado (n = 5), engrosamiento pared colédoco (n = 2), masa tumoral (n = 3), halo periférico (n = 2). Diagnósticos citohistológicos: infiltrado linfoplasmocitario (n = 3), muestra benigna inflamatoria (n = 7), atipia (n = 1), insuficiente (n = 1). La sensibilidad, especificidad y precisión diagnóstica de la punción en diferenciar malignidad de benignidad fue del 50%, 100% y 91,6% respectivamente. De acuerdo con la revisión de los criterios diagnósticos clínicos japoneses, hubo 9 casos indicativos de PAI. Resto de pacientes: 3 pancreatitis crónica por otras causas, 2 adenocarcinomas, 1 cirrosis biliar primaria. Hubo 1 falso negativo de adenocarcinoma no detectado por imagen USE ni punción. No se identificaron complicaciones asociadas a la punción. Conclusiones: la ecoendoscopia es segura y útil en el manejo diagnóstico de pacientes con sospecha de PAI. Existen unos signos por imagen USE específicos que apoyan la sospecha inicial. La punción es segura y útil con la finalidad de excluir malignidad.
AB0636 Alteration of vitamin d after a whole body uv-b exposure in context of a diet
Authors: M. Majer, M. Biersack, H. Piazena, T. Braun, V. Höhne-Zimmer, G.-R. Burmester, F. Buttgereit, R. Uebelhack, J. Detert
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> In the European population of northern climes poses the deficiency of vitamin D (vitD) a frequent problem, especially in autumn and winter<sup>1,2</sup>. On the other hand it is difficult to supply a necessary dose of vitD in a diet<sup>1</sup>. The substitution in case of deficiency of vitD occurs principally orally<sup>3</sup>. <h3>Objectives</h3> The aim of this pilot project was to investigate, if 1) an UV-B-stimulus and 2) a diet rich in vitD have an influence on vitD level in autumn and winter months. <h3>Methods</h3> 20 healthy female subjects (age: 21-25 years, UV skin types: I - III ) received 3 whole body irradiation with an solar simulated UV-B-stimulus on 3, not successive days, within one week in winter 2011/2012. The dose of the UV-B-stimulus came to 40%, 60% and 75% of the minimal erythema dose (MED) according to UV skin type classification. The level of vitD-metabolites, 25-hydroxy-vitD (25-OH-vitD) and 1.25-Dihydroxy-vitD (1.25-diOH-vitD) were measured on day (d) 1, 8, 36 and 50 (before the irradiation, 3 d, 4 and 6 weeks after the irradiation). A questionnaire including food examples rich of vitD has been enquired on d1. <h3>Results</h3> The level of both vitD-metabolites increased significantly on d8 (25-OH-vitD - p&lt;0,001 and 1.25-diOH-vitD – p=0,009). On d36 and d50 the level of 25-OH-vitD was also higher than baseline level ( p &lt; 0,001 on d36, p = 0,043 on d50). There was no correlation between a diet rich in vitD and the beginning level of 25-OH-vitD (k=0,17). <h3>Conclusions</h3> Calculated whole body UV-B-irradiation resulted in a significant and long-lasting increase of the level of vitD. A correlation between a diet rich in vitD and the beginning level of 25-OH-vitD couldn’t be shown. It is necessary to investigate if UV-B-stimulus could be used as an alternative to an oral substitution in case of deficiency of vitD. <h3>References</h3> Referenzwerte für die Nährstoffzufuhr. Vitamin D. Deutsche Gesellschaft für Ernährung (DGE), 1. Auflage, 4. korrigierter Nachdruck 2012 Webb AR, Engelsen O, Calculated ultraviolet exposure levels for a healthy vitamin D status. Photochem Photobiol, 2006;821:697-703 Chandra P, Wolfenden LL, Ziegler TR et al Treatment of vitamin D deficiency with UV light in patients with malabsorption syndromes: a case series. Photodermatol Photoimmunol Photomed 2007;5:179-185 <h3>Disclosure of Interest</h3> None Declared
Hepatitis without Jaundice and without Hepatomegaly
Authors: T. J. Domenici
Journal: New England Journal of Medicine (1949)

FOUR cases of hepatitis without jaundice and without hepatomegaly constitute the material of this report. Hepatitis without jaundice has been variously described as a "mild disease"1 and "mild non-icteric form of hepatitis,"2 running a course of six to eight weeks. A review of the literature reveals that an enlarged and tender liver is an essential finding in virus hepatitis and in the hepatitis seen in infectious mononucleosis. The cases presented below were severe illnesses running a four to six months' course. The liver was not enlarged, but instead a sharply circumscribed area of localized tenderness in the right upper quadrant . . .
Effect of Calcium Gluconate and Adrenal Steroids on Sodium and Water Excretion in Patients with Cirrhosis and Ascites
Authors: Joseph F. Dingman, Harry F. Yoffee
Journal: New England Journal of Medicine (1960)

IN recent years, several workers1 2 3 have shown that the intravenous administration of calcium salts to normal man and animals frequently results in sodium and water diuresis. Studies in this laboratory of the effects of calcium gluconate on the antidiuretic action of vasopressin4 confirmed the increased sodium excretion and suggested that intravenous calcium therapy may have salutary effects in patients with sodium-retaining disorders. Patients with cirrhosis and ascites were selected for therapeutic trials since they usually do not require digitalis treatment, which may make calcium infusions hazardous, and also do not have intrinsic renal disorders that might prevent proper excretion of . . .
Untoward Reactions to Lysergic Acid Diethylamide (LSD) Resulting in Hospitalization
Authors: William A. Frosch, Edwin S. Robbins, Marvin Stern
Journal: New England Journal of Medicine (1965)

MOST typically, medical research has proceeded from clinical observation to clinical investigation to laboratory experiment. Some of the striking exceptions to this pattern have been studies of a variety of pharmacologic agents that are capable of producing changes in psychic state. These drugs, first isolated or synthesized in the laboratory, occasionally create a new clinical syndrome or a new etiology of an old syndrome as an undesirable by-product of individual abuse or poor judgment by the physician.A sudden surge of admissions to the Bellevue Psychiatric Division after ingestion of d-lysergic acid diethylamide (LSD) prompted us to review the history . . .
How Far Do You Go? Intensive Care in a Resource-Poor Setting
Authors: Antonia P Eyssallenne
Journal: New England Journal of Medicine (2012)

A 12-year-old girl arrives unresponsive in a Port-au-Prince emergency department, with labored breathing and right hemiplegia. In one of the few functioning ICUs in Haiti, premature death is no longer automatic. But in such an environment, how far do you go to extend life?
Prognosis in BRCA1, BRCA2 associated breast cancer (BC): a prospective Breast Cancer Family Registry (BCFR) international population-based cohort study.
Authors: P Goodwin, K Phillips, D West, M Ennis, J Hopper, EM John, F O'Malley, R Milne, I Andrulis, M Friedlander, T Longacre
Journal: Cancer Research (2009)

Abstract Abstract #2072 Hereditary BC occurs at a younger age and is associated with more adverse tumor-related features than sporadic breast cancer (BC) (defined here as BC in those with no 1st or 2nd degree family history of breast or ovarian cancer). Using pre-specified criteria, we assembled a population-based cohort of newly diagnosed BC at 3 centers: Ontario, Canada (1996-98), San Francisco Bay area, USA (1995-2000), Melbourne/Sydney, Australia (1991-1998). Medical information was obtained from medical records; women were followed prospectively for recurrence, new cancers and death. Pathology data were obtained from central review or pathology reports. BRCA1 and BRCA2 mutation testing was performed on 77% and 70% of cases, respectively (sporadic BC cases were not tested at 2 centers). Hereditary and sporadic BC cases were compared using Cox proportional hazards (stratified by center). 3215 eligible cases were enrolled in the BCFR, with a mean age at diagnosis of 46.9 years. Median follow-up was 7.61 years; 565 women had distant recurrences and 547 died. There were 92 cases with BRCA1 and 72 with BRCA2 mutations; 1549 (48.2%) had sporadic BC; the remainder had familial BC as defined above. BRCA1 mutations were associated with young age, estrogen and progesterone receptor (ER and PgR) negativity and high grade; BRCA2 mutations were associated with node positivity and high grade. Distant disease-free survival (DDFS) and overall survival (OS) did not differ significantly between BRCA1 carriers and sporadic cases in univariate or multivariate analyses. DDFS and OS were worse in BRCA2 carriers than in sporadic cases (HR 1.6, p=0.04 and HR 1.8, p=0.01, respectively) in univariate analyses but not in multivariate analyses (DDFS HR 1.0, p=0.98; OS HR 1.13, p=0.61). The small group of BRCA2 carriers who did not receive adjuvant chemotherapy had a significantly worse OS (multivariate HR 3.63, p = 0.005). Furthermore, BRCA2 carriers who received adjuvant tamoxifen had significantly worse OS than women with sporadic BC (HR=2.0, p=0.03). We conclude that BRCA1 and BRCA2 mutations do not independently impact DDFS or OS. Significantly worse outcomes were seen in BRCA2 carrier subgroups defined by adjuvant treatment; this requires further investigation and may have implications for clinical practice. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2072.
Abstract 5614: Interleukin-10 inhibits the induction of macrophage cytotoxicity against bladder cancer cells by Mycobacterium bovis bacillus Calmette-Guérin (BCG)
Authors: Yi Luo, Ruifa Han, David P. Evanoff, Xiaohong Chen
Journal: Cancer Research (2010)

Abstract Intravesical BCG therapy has been used for the treatment of superficial bladder cancer for three decades. However, the mechanisms underlying BCG therapy currently remain elusive. We have focused on BCG induction of macrophage cytotoxicity against bladder cancer cells. Previously, we observed that macrophages are cytotoxic to bladder cancer cells upon stimulation with BCG in vitro. However, we found that macrophages from C57BL/6 mice are less potent than those from C3H/HeN mice for the killing of both bladder cancer MBT-2 cells and MB49 cells. This study was to determine whether macrophage-derived interleukin (IL)-10 is responsible for this discrepancy between these two commonly used murine bladder cancer models. Thioglycollate-elicited peritoneal exudate cells were harvested from mice 3 days after intraperitoneal injection of 2 ml 3% thioglycollate. Cells were incubated for 3 hours and non-adherent cells were removed after incubation. The remaining cells were 96% F4/80-positive cells as determined by flow cytometry. The prepared macrophages were then used for the analysis of BCG induction of cytotoxicity, cytokines, and nitric oxide (NO) in vitro. Studies demonstrated that BCG-stimulated C57BL/6 macrophages produced a substantially high level of IL-10 compared to BCG-stimulated C3H/HeN macrophages. This high IL-10 production correlated with reduced production of tumor necrosis factor (TNF)-α, IL-6 and NO in BCG-stimulated C57BL/6 macrophages. Neutralizing endogenous IL-10 during BCG stimulation increased C57BL/6 macrophage cytotoxicity against MB49 cells by 3.2-fold, along with increased production of TNF-α by 6.4-fold and NO by 3.6-fold, respectively. Macrophages from genetically modified C57BL/6 mice lacking IL-10 (IL-10−/−) also exhibited increased killing of MB49 cells and production of TNF-α and NO upon BCG stimulation. In addition, supplementation of exogenous recombinant IL-10 reduced BCG-induced C3H/HeN macrophage cytotoxicity against both MBT-2 cells and MB49 cells in a dose-dependent manner. Taken together, our results reveal the inhibitory role of IL-10 in BCG-induced macrophage cytotoxicity, suggesting that blockage of IL-10 may potentially enhance the effect of BCG in the treatment of bladder cancer patients, particularly for BCG non-responders who are often associated with high IL-10 production in response to BCG treatment. 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 5614.
Abstract 4552: Utilization of pathway activation and somatic mutation analysis in combination in fine needle aspirates to identify candidate drugs for effective treatment of breast cancer
Authors: Tani Lee, Phillip S. Kim, Gulia Harvie, Gary Meyer, Glen Leesman, Emma Langley, Limin Liu, Hicholas Hoe, Fred Princen, Fabiyola Selvaraj, Xinjun Liu, Sharat Singh
Journal: Cancer Research (2012)

Abstract A critical hurdle in implementing prognostic and predictive biomarkers in clinical trials is our inability to perform an efficient molecular characterization of the limited amounts of available clinical samples. Here we report a comprehensive molecular analysis of fine needle aspirate (FNA) samples collected from metastatic sites of 58 breast cancer (BCA) patients. The analysis included interrogation of key receptor tyrosine kinases and their downstream signaling molecules including HER1, HER2, p95HER2, HER3, cMET, IGF1R, PI3K, Shc, AKT and ERK as well as oncogenic somatic mutational profiling. A multiplexed immunoarray CEER™ (Collaborative Enzyme Enhanced Reactive-immunoassay) platform was utilized to determine the levels of pathway protein expression and phosphorylation. All FNA collections provided sufficient materials for the combined analysis of multiplexed pathway expression/activation and somatic mutation analysis. All the FNA from metastatic sites (mFNA) collected from HER2 positive primary tumors (determined by IHC) were also CEER-HER2 positive. Over-expression of HER2 was found in 10% of mFNAs collected from BCA patients with HER2 negative primary tumors. PIK3CA mutations were found in 20% of the samples in this cohort. Statistically significant higher levels of phosphorylated AKT, ERK (downstream effector targets) as well as HER1, HER2, HER3 and IGF1R (PI3K membrane recruiter proteins) were found in mFNAs with PIK3CA mutations. Subset of PIK3CA wildtype patients also showed robust pathway signature. Hence, evaluation of biomarkers in BCA patients should include both pathway proteins as well as mutation analysis. A comprehensive disease profiling can provide insightful information on efficacy of specific agents on its intended target protein inhibition. As CEER requires minimal amount of specimen, performance of routine pathway profiling can be achieved in clinical settings. A multiplexed pathway analysis can also provide valuable information about potential drug resistance mechanisms. Furthermore, a combined mutational and pathway activation profiling can guide therapeutic strategies in clinical setting. 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 4552. doi:1538-7445.AM2012-4552
CD103+ Kidney Dendritic Cells Protect against Crescentic GN by Maintaining IL-10–Producing Regulatory T Cells
Authors: Beatrix D.G. Evers, Daniel R. Engel, Alexander M.C. Böhner, André P. Tittel, Torsten A. Krause, Christoph Heuser, Natalio Garbi, Wolfgang Kastenmüller, Matthias Mack, Gisa Tiegs, Ulf Panzer, Peter Boor, Isis Ludwig-Portugall, Christian Kurts
Journal: Journal of the American Society of Nephrology (2016)

Kidney dendritic cells (DCs) regulate nephritogenic T cell responses. Most kidney DCs belong to the CD11b+ subset and promote crescentic GN (cGN). The function of the CD103+ subset, which represents <5% of kidney DCs, is poorly understood. We studied the role of CD103+ DCs in cGN using several lines of genetically modified mice that allowed us to reduce the number of these cells. In all lines, we detected a reduction of FoxP3+ intrarenal regulatory T cells (Tregs), which protect against cGN. Mice lacking the transcription factor Batf3 had a more profound reduction of CD103+ DCs and Tregs than did the other lines used, and showed the most profound aggravation of cGN. The conditional reduction of CD103+ DC numbers by 50% in Langerin-DTR mice halved Treg numbers, which did not suffice to significantly aggravate cGN. Mice lacking the cytokine Flt3L had fewer CD103+ DCs and Tregs than Langerin-DTR mice but exhibited milder cGN than did Batf3-/- mice presumably because proinflammatory CD11b+ DCs were somewhat depleted as well. Conversely, Flt3L supplementation increased the number of CD103+ DCs and Tregs, but also of proinflammatory CD11b+ DCs. On antibody-mediated removal of CD11b+ DCs, Flt3L supplementation ameliorated cGN. Mechanistically, CD103+ DCs caused cocultured T cells to differentiate into Tregs and produced the chemokine CCL20, which is known to attract Tregs into the kidney. Our findings show that CD103+ DCs foster intrarenal FoxP3+ Treg accumulation, thereby antagonizing proinflammatory CD11b+ DCs. Thus, increasing CD103+ DC numbers or functionality might be advantageous in cGN.