tbuckley/cabot-search huggingface dataset:
Abstract 1259: Murine HLA-restricted CD4+ T cell lines as source of high affinity TCRs specific for the human breast cancer-associated tumor antigen NY-BR-1.
Authors: Adriane Gardyan, Wolfram Osen, Stefan B. Eichmüller, Inka Zoernig, Dirk Jaeger
Journal: Cancer Research (2013)

Abstract Out of all malignancies, breast cancer is the second most common cancer worldwide and the leading cause of cancer death in females. Passive immunization approaches such as adoptive transfer of TCR-transduced autologous T cells specific for tumor associated antigens, provide an innovative strategy for cancer immunotherapy. The differentiation antigen NY-BR-1 has been described to be expressed in 60% of all invasive mammary carcinomas. Since NY-BR-1 protein levels are highly elevated in malignant breast tissues compared to healthy breast tissue, NY-BR-1 might represent a suitable target antigen for T cell based immunotherapy approaches against breast cancer. Successful immunological eradication of tumors depends on the presence of activated tumor antigen-specific CD4+ effector T cells as documented by numerous reports. Therefore, NY-BR-1 was screened for the presence of CD4+ T cell epitopes using HLA-transgenic mice immunized with a NY-BR-1-encoding expression plasmid and subsequent ex vivo analysis of the NY-BR-1-specific T cell responses against a synthetic peptide library covering the entire NY-BR-1 protein. Stable CD4+ T cell lines specific for six newly identified epitopes could be established from peptide-immunized DRB1*0301 and HLA-DRB1*0401-transgenic mice and HLA-DR-restriction of the cell lines was confirmed on peptide loaded T2/DR3 and T2/DR4 target cells. Next, natural processing of the epitopes identified in HLA transgenic mice will be tested in the human system using human HLA-matched cells lines infected with NY-BR-1 encoding adenovirus as targets for recognition by the murine NY-BR-1-specific CD4+ T cell lines. Clinical relevance of the newly identified NY-BR-1-specific epitopes will be investigated by screening of blood samples from NY-BR-1+, HLA-matched breast cancer patients for the presence of cognate CD4+ T cells. High affinity TCRs from NY-BR-1 specific CD4+ T cells will be sequenced and subsequently used to generate autologous TCR-transduced T cell lines ready for adoptive transfer of breast cancer patients Citation Format: Adriane Gardyan, Wolfram Osen, Stefan B. Eichmüller, Inka Zoernig, Dirk Jaeger. Murine HLA-restricted CD4+ T cell lines as source of high affinity TCRs specific for the human breast cancer-associated tumor antigen NY-BR-1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1259. doi:10.1158/1538-7445.AM2013-1259
Abstract 4799: Identification of drug resistance targets in ovarian cancer using a proteomic approach
Authors: Isa Cruz, Rita Angelino, Helen Coley, Andreas Schatzlein, Min Yang
Journal: Cancer Research (2012)

Abstract Ovarian cancer ranks first in the number of deaths and second in the number of new cases among gynecological cancers. In the majority of the cases, surgery is the intervention of choice, but chemotherapy has progressed considerably over the last years. First-line treatment for advanced-stage disease is a combination of carboplatin and paclitaxel. However, drug resistance has become a major obstacle to the successful chemotherapeutic treatment of human cancers. Currently, there is no clear consensus on treatment options for ovarian cancer patients who acquired drug resistance, due to the lack of knowledge about drug resistance mechanisms. There is an urgent need to explain how drug resistance occurs and to identify proteins related to this phenomenon, so that inhibitors can be designed. The aims of this study are to develop and optimise a two-dimensional gel electrophoresis method to compare protein profile of human ovarian cancer cell lines, which are sensitive or resistant to anticancer chemotherapy, so that proteins related to drug resistance can be identified using mass spectrometry. The parental ovarian cancer cell line models PEO1 and SKOV-3 are used as drug sensitive reference cell lines. Novel drug resistant models, derived from the parental lines, with in vitro acquired resistance to paclitaxel and carboplatin are used alongside their respective drug sensitive parental counterparts. Proteins related to tumorigenesis or drug resistance, either new or previously reported, were identified in at least one of the three cell lines. These proteins belong to different classes and are responsible for distinct functions within the cell, such as cytoskeleton and cell structure, detoxification and stress response, and cellular metabolism. This is the first proteomic study on these specific ovarian cancer cell lines using paclitaxel and carboplatin. The results obtained will be useful for further studies of resistance mechanisms and screening of resistance biomarkers for the development of tailored therapeutic strategies. 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 4799. doi:1538-7445.AM2012-4799
SP0169 The Pain-Immune AXIS
Authors: S. B. McMahon
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> Chronic pain remains an area of great unmet medical need, with epidemiological studies finding a prevalence of about 20% in Europe and the US and large numbers of these failing to receive adequate relief from existing therapies. Several possible new opportunities to develop analgesic drugs have emerged from a realisation of the importance of the immune system in driving chronic pain responses. One body of evidence relates to the role of peripheral inflammatory processes in chronic pain. While this role has been long appreciated (pain is one of the cardinal defining features of inflammation) only recently has there been recognition of novel peripheral pain meditators being identified originating from immune cells. The most clinically advanced data relates to the role of NGF (nerve growth factor) but recent data also suggests the important role played by several chemokines. A second area of current interest lies in the role of the CNS microglia in pain. Long regarded as passive surveyors of tissue environment, it now appears that they can in some circumstances (particularly associated with peripheral nerve injury) become highly reactive and the source of several centrally acting pain mediators – molecules that alter pre- and/or post-synaptic processing of pain-related stimuli. These developments will be reviewed in this lecture. <h3>Disclosure of Interest</h3> None Declared
1128 PREDICTION MODEL OF ANEMIA USING ITPA GENOTYPE IDENTIFIES PATIENTS AT HIGH RISK OF ANEMIA AND TREATMENT FAILURE WITH PEGYLATED-INTERFERON PLUS RIBAVIRIN FOR CHRONIC HEPATITIS C
Authors: M. Kurosaki, J. Itakura, K. Tsuchiya, H. Nakanishi, Y. Asahina, M. Mizokami, Y. Tanaka, N. Izumi
Journal: Journal of Hepatology (2012)
P953 DOES RIFAXIMIN REDUCE THE RISK OF SPONTANEOUS BACTERIAL PERITONITIS IN CIRRHOTIC PATIENTS WITH REFRACTORY ASCITIS?
Authors: R.S. Munteanu Danulescu, A. Ciobica, O.C. Munteanu Danulescu, A. Trifan, C. Stanciu, C. Cojocariu
Journal: Journal of Hepatology (2014)
Abstract 3063: Novel putative tumor suppressor LZAP binds and regulates Wip1
Authors: Hanbing An, Xinyuan Lu, Wendell G. Yarbrough
Journal: Cancer Research (2010)

Abstract Our group has shown that LZAP is lost in ∼30% of head and neck squamous cell carcinomas and that inhibition of LZAP expression is associated cellular transformation and xenograft tumor growth. LZAP increases invasion and inhibits cellular proliferation and clonogenic growth mediated correlating with inhibition of NF-kB and activation of p53. Other researchers have found that LZAP promotes cell death in response to cytotoxic therapy at least partially dependent on activation of Cdk1 through Chk1/2 inhibition. We have also found that LZAP binds and inhibits p38 and this inhibition does not depend on upstream regulators MKK3 and MKK6. The activity of MAPKs reflects a balance between the upstream activating kinases and inactivating protein phosphatases. Since LZAP inhibition of p38 is not through upstream kinases, we determined if phosphatase activity targeting p38 was regulated by LZAP. Wip1 is a major phosphatase regulating p38 phosphorylation and activation. Wip1 is a member of the PP2C family of serine/threonine phosphatases and was identified in a screen to detect p53 responsive genes. We noted that LZAP and Wip1 had many binding partners/targets including RelA, p38, and Chk1/Chk2 in common. Mechanisms of LZAP inhibition of RelA, p38 and Chk1/Chk2 are not well described, but expression of LZAP is associated with decreased phosphorylation of all three target proteins. To determine if LZAP could regulate Wip1 activity, we first evaluated LZAP and Wip1 interaction through immuno- or affinity precipitation. LZAP and Wip1 co-precipitated after expression in mammalian cells and bacterially expressed LZAP pulled down Wip1 generated through in vitro transcription and translation. After transient expression in mammalian cells, Wip1 and LZAP co-localized by indirect immunofluorescence staining. When expressed singly, Flag-tagged Wip1 localized to the nucleus and LZAP was excluded from the nucleolus, but localized to both cytoplasm and nucleus. When Wip1 and LZAP were co-expressed LZAP localization was altered so that nucleolar LZAP was observed. These findings indicate that co-expression of LZAP and Wip1 results in alternation of LZAP subcellular localization with resultant co-localization of these two proteins to nucleus. Functionally, co-expression of LZAP with Wip1 increased Wip1 content within p38 immunocomplexes which was associated with decreased p38 phosphorylation. Together, our findings indicate LZAP binds and co-localizes with Wip1 and increases activity of Wip1 towards p38. Wip1 may play a common mediator for LZAP activities. 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 3063.
OP0131 Upregulation of Immunoproteasome Subunits PSMB8 and PSMB9 in Myositis Indicates Active Inflammation with Involvement of Antigen Presenting Cells, CD8+ T-Cells and IFN Gamma
Authors: K.M. Ghannam, L. Martinez Gamboa, L. Spengler, S. Krause, B. Smiljanovic, M. Bonin, A. Grützkau, G.-R. Burmester, T. Häupl, E. Feist
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. <h3>Objectives</h3> To decipher the role of proteasome in myositis, we investigated the expression of catalytic proteasomal subunits in individual cell types and muscle tissues and focused on possible immune triggers. <h3>Methods</h3> Expression of constitutive (PSMB5, -6, -7) and corresponding immunoproteasomal subunits (PSMB8, -9, -10) was analyzed by real-time PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. <h3>Results</h3> Real-time PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8, -9, -10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were also elevated in IIM compared to NIM and even more than in matched blood samples. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed high-ranking upregulation of these immunosubunits in IIM including strong association with molecular disease activity and identified antigen processing and presentation as involved pathways. Comparison with reference profiles of sorted immune cell types and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1 and IRF1 expression and was associated with interferon gamma. The strong elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. <h3>Conclusions</h3> Immunoproteasomes indicate that antigen processing is dominantly involved in the pathophysiology of active IIM. Association with antigen presenting cells, T-cells, CD8 and IFN gamma suggests perpetuating crosstalk sustained by antigen processing. Therefore, these diseases may exemplarily qualify for the evolving therapeutic concepts of immunoproteasome specific inhibition. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3161
Case 18-1997
Authors: Michael V. Seiden, Robin E. Kirby
Journal: New England Journal of Medicine (1997)

Presentation of CaseA 78-year-old man was admitted to the hospital because of a stricture of the sigmoid colon.Five years earlier, a rectal mass had been found on a routine sigmoidoscopic examination. An examination with a flexible sigmoidoscope showed a sessile, slightly lobulated, polypoid mass, 3 cm in diameter, just within the anal sphincter. Microscopical examination of biopsy specimens suggested a solitary rectal ulcer. The carcinoembryonic antigen level was 1.2 μg per liter. A transanal excision of the mass was performed, and microscopical examination of the specimen confirmed the diagnosis of a rectal ulcer. Follow-up examinations with a flexible . . .
Researchers Turn to Canine Clinical Trials to Advance Cancer Therapies
Authors: Julie A. Jacob
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
P68 Outcome of a Pragmatic Protocol For CT Lung Nodule Surveillance in a UK District General Hospital
Authors: MT Reichmann, D Edwards, A Sivaloganathan, A Drury, D Laws
Journal: Thorax (2012)

<h3>Introduction and objectives</h3> The appropriate way to follow-up indeterminate pulmonary nodules found incidentally on CT scanning has caused clinicians and radiologists in the UK some concern. Guidelines developed by the Fleischner Society in 2005 were based on studies outside of the UK. Our hospital developed local guidance for lung nodule surveillance prior to the publication of Fleischner guidelines which were designed to be pragmatic and easy to follow. We present the results of our experience. <h3>Methods</h3> Outcomes of patients undergoing the local lung nodule surveillance programme in our hospital from 2004 to 2011 were analysed. Eligibility criteria included initial lung nodules 5–10mm diameter; previous or current smokers; aged 45–75 years old with good performance status. Those with 5 or more nodules more than 5mm diameter, benign calcification, or patients already under follow up, e.g. oncology patients, were excluded. A stamp was placed in the notes and on CT request forms to record and remind clinicians of the criteria. In accordance to our protocol CT scans were performed at 6, 18 and 30 months from the index scan. <h3>Results</h3> 107 patients were followed up but only 63 patients fulfilled the initial inclusion criteria. This shows that despite a pragmatic protocol, clinicians will often interpret it differently when faced with an individual. The commonest reason was nodule size over 10mm. Of those eligible, the outcomes were recorded as to whether nodule confirmed as cancer (positive), nodule size reduced or unchanged over 30 months (negative), surveillance cut short as a clinical decision and those still under surveillance. Of the 63 patients, 2 were found to have lung cancer (see Figure 1). Of those patients who were not eligible, but still underwent the surveillance programme, 6 were found to have cancer. These were not eligible because nodule size was over 10mm. <h3>Conclusions</h3> Our study shows that a simple protocol is helpful to clinicians, but will be adapted according to the clinicians’ belief. In our study 3% of nodules 5–10mm were early cancers. Nodules over 10mm, which were bigger than our criteria but followed up within this protocol, were more likely to be cancerous (14%).
931 PREDICTION OF LONG-TERM SURVIVAL IN CHRONIC HEPATITIS C PATIENTS WITH ADVANCED FIBROSIS USING STANDARD LABORATORY TESTS
Authors: A.J.P. van der Meer, B.E. Hansen, J.J. Feld, H. Wedemeyer, J.-F. Dufour, F. Lammert, A. Duarte-Rojo, M.P. Manns, L. Kuske, S. Zeuzem, W.P. Hofmann, R.J. de Knegt, B.J. Veldt, H.L.A. Janssen
Journal: Journal of Hepatology (2012)
Relationship Between Hypertension and Proteinuria Associated with Bevacizumab : Retrospective Study on Cardiac Toxicity
Authors: K. Komori, M. Mukai, C. Ishitoko, K. Sugitani, Y. Nakata, G. Tei, Y. Masu, W. Shioyama, N. Awata, M. Hori
Journal: Annals of Oncology (2013)
Impact of radiofrequency ablation for Barrett's esophagus on quality of life
Authors: E. Akbal, S. Köklü, A. Babalı
Journal: Endoscopy (2011)

In a recent study published in Endoscopy, Shaheen et al. compared endoscopic radiofrequency ablation (RFA) with a sham procedure with regard to quality of life (QoL) in patients with Barrett’ esophagus [1]. They concluded that patients receiving RFA had a better QoL compared with patients undergoing the sham procedure. Moreover their study showed significantly lower depression, general worry, stress, worry about esophageal cancer and esophagectomy, dissatisfaction about the condition of their esophagus, and impact on work and family life in the RFA group. However, there are some methodological errors.
Is the second-step conditionalization unnecessary?
Authors: In-mao Liu
Journal: Behavioral and Brain Sciences (2009)

Abstract Because the addition of the conditional premise tends to increase modus ponens (MP) inferences, Oaksford &amp; Chater argue that the additional knowledge is assimilated to world knowledge before the Ramsey test is carried out to evaluate P ( q | p ), so that the process of applying the Ramsey test could become indistinguishable from the process of applying the second-step conditionalization.
Abstract 3115: Sumoylation enhances the stability of the proto-oncogene EVI1 however negatively regulates its DNA binding and transcriptional activity.
Authors: Sneha Singh, Soumen Chakraborty
Journal: Cancer Research (2013)

Abstract Aberrant expression of the proto-oncogene EVI1 (Ecotropic virus integration site1) has been implicated not only in lymphoid or myeloid malignancies but also in several other solid tumors like colon, ovarian and breast cancer. Despite its crucial role in oncogenesis, the regulatory factors and mechanisms that control the function of EVI1 are partially known. Post translational modifications play a crucial role in regulating various cellular processes by controlling the function of several proteins. Here we show that EVI1, a transcription factor is post-translationally modified by SUMO1. Indirect immunofluorescence studies revealed that EVI1 and SUMO1 colocalized in the nuclear speckles in the cells transiently transfected with EVI1 and SUMO1 as well as cells that constitutively expresses EVI1. Sumoylation is known to stabilize their target protein which was also observed in case of EVI1 through pulse chase assay with cycloheximide. Reporter gene assay revealed that sumoylation impaired EVI1 mediated transactivation of Bcl-xL and SIRT1 promoters and also reduced the DNA binding efficiency of EVI1 which was confirmed through ChIP assay. PIAS proteins are known as SUMO E3 ligase which enhances the sumoylation of the proteins. PIAS proteins are also known to regulate the function of several proteins independent of its ligase activity. Co-immunoprecipiation assay revealed that EVI1 directly interacts with SUMO E3 ligase PIASy, which was also found to enhance EVI1 sumoylation. Our study also demonstrates that PIASy negatively regulated EVI1 transcription activity which is independent of its ligase activity. Thus PIASy was found to be an interacting partner that regulates the function of EVI1 in sumoylation dependent as well as independent manner. In summary, we present a new modifier of EVI1 which controls its stability and deregulates its transcriptional activity. Further study in context with EVI1-SUMO1-PIASy may give a better idea in understanding the functions and the regulation of EVI1 in normal and diseased cells. Citation Format: Sneha Singh, Soumen Chakraborty. Sumoylation enhances the stability of the proto-oncogene EVI1 however negatively regulates its DNA binding and transcriptional activity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3115. doi:10.1158/1538-7445.AM2013-3115
Whistling in the Dark
Authors: Anand Vaidya, Daniel A. Solomon, Christopher H. Fanta
Journal: New England Journal of Medicine (2012)

A 38-year-old woman in Florida presented to her primary care physician with shortness of breath, fever, and a cough productive of yellow sputum. She was treated empirically with antibiotics for a presumed respiratory tract infection, and her symptoms resolved. She returned a few weeks later with an intermittent, nonproductive cough, shortness of breath, wheezing, and retrosternal burning. . . .