tbuckley/cabot-search huggingface dataset:
Abstract 1937: Enhanced tumor control with adoptive transfer of TCR engineered T cells expressing Tcl1
Authors: Richard C. Koya, Stephen Mok, Thinle Chodon, Michael Teitell, Antoni Ribas
Journal: Cancer Research (2010)

Abstract Advanced stage melanoma is associated with notable resistance to radio and chemotherapy, warranting intense research for new treatments. Immunotherapy with adoptive transfer of antigen-specific T cells has shown anti-tumor activity in melanoma, but questions remain regarding the biology of T cell responses, and the necessary enhancement strategies to achieve significant impact in the overall clinical outcome. The14 kDa protein T cell leukemia-1 (TCL1) has shown to augment the growth and survival of mature but not immature T cells through enhancement of signals that operate through the PI3K-Akt and protein kinase C (PKC)-MAPK- ERK pathways. Here we engineered TCL1 transgenic lymphocytes to express a T cell receptor (TCR) specific to ovalbumin antigen to be used in an adoptive transfer model for melanoma tumor control in vivo. A bicistronic MSCV-based retroviral vector was engineered to express the alpha and beta chains of a TCR (OT1) specific for SIINFEKL peptide of ovalbumin (OVA) presented on mouse MHC I (Kb). The transgenes were interspaced with picornavirus-derived highly efficient self-cleaving 2A-like sequences to allow balanced protein expression. Transduction of ex vivo activated primary murine T cells with retrovirus stocks demonstrated correct expression of specific TCR as analyzed by flow-cytometry with anti-Valpha2/Vbeta5.1+5.2 staining and OVA (SIINFEKL) tetramer assays, with transduction efficiency of 64.8-76% at M.O.I.=20. OT1 TCR-transduced murine splenocytes from TCL1 transgenic mice stimulated with ovalbumin-expressing murine EL4 lymphoma or B16 melanoma showed high and specific IFNgamma production (30,000 and 16,000 pg/ml/1e6cells/24h respectively) as assessed by ELISA. In vivo studies were carried out in C57BL6 mice implanted with syngeneic B16/OVA murine melanoma. Intravenously adoptive transferred OT1 TCR-transduced splenocytes from TCL1 transgenic mice lead to higher survival and tumor size control in comparison to OT1 TCR-transduced control syngeneic splenocytes (tumor volume: 221.65mm3 and 1095.48mm3, respectively at day 23 post-infusion, p&amp;lt;0.05). In conclusion, TCL1 expression in mature T cells enhanced the potency of adoptively transferred T cells for treatment of melanoma. 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 1937.
SP0042 Future challenges for health professionals: Communication across health care levels
Authors: B. Prodinger
Journal: Annals of the Rheumatic Diseases (2013)

Delays in seeking primary care lead to late referrals to secondary care in people with rheumatoid arthritis, which in turn may impact on treatment outcomes. To ensure timely, comprehensive, and continuous care for people with rheumatoid arthritis, the role of health professionals in primary and secondary care is complex goes beyond the treatment of disease-related symptoms and entails supporting people with rheumatoid arthritis in managing their daily lives and enabling them to participate in work and social life. Such provision of care may challenge or might be challenged within systems that are predominantly structured around the treatment of disease-related symptoms. Communication and collaboration of health professionals within and across care levels becomes then even more important. Some of the challenges in communicating across care levels include existing processes and structures that regulate the interface between primary and secondary care and services that can be made accountable at each care level. For instance information exchange across health professionals and care levels might be something that cannot be made accountable within certain institutional processes and structures. In this lecture I draw upon an ongoing comparative institutional ethnographical study about routine treatment processes in the provision of care to patients with rheumatoid arthritis in Austria, Sweden, and the UK. The insights gained from this study exemplify how processes and structures, which regulate the interface of primary and secondary care and the scope of practices at each level, differ in the three countries and open up varying possibilities and challenges for communication across care levels. This lecture concludes with some reflections based on this comparative study and opens up for discussion how communication across care levels can be facilitated and fostered while remaining sensitive to the varying possibilities and challenges that health professionals in different countries face in their daily practices. <h3>Disclosure of Interest</h3> None Declared
Hutchinson's Nail Sign
Authors: Sook Jung Yun, Seong-Jin Kim
Journal: New England Journal of Medicine (2011)

A 37-year-old man presented with a brownish-black nail on the great toe of the right foot. A darkly pigmented linear patch had started to form within the toenail 4 years earlier and had widened and darkened over time. Two months before the current presentation, the dark pigment had begun to involve the hyponychium and the proximal and lateral nail folds. The patient's personal and family medical histories were otherwise unremarkable. The results on routine laboratory testing were within normal limits. An incisional biopsy of the nail matrix showed atypical melanocytes and inflammatory cells along the basal layer of the epidermis, . . .
Abstract 4970: Folate metabolism defect induce invasion and Gefinitib resistance in lung cancer.
Authors: Chun-Te Ho, Tsan-Zon Liu, Yu-Ting Chou, Shih-Hsin Hsiao, Jun-Jen Liu
Journal: Cancer Research (2013)

Abstract Folate, act as an one-carbon units donator or acceptor, participate in numerous biochemical reactions. Because mammals can't synthesize folic acid de novo, obtain from diet or from microbial breakdown in the gut is essential. Pathological study revealed that tumor cell expressing high level of folate receptors (FR) comparing to normal tissue. Therefore, exploring the application of folate-related physiological properties as an anticancer strategy arose worldwide interesting. Previous studies in lung cancer revealed a positive correlation in folate receptors overexpression and efficacy of antifolate chemotherapy. Here we describe prolong Alimta treatment would prompt lung cancer cell's malignancy. Cultivation of lung cancer CL1-0, CL1-5, and A549 in low dose Alimta (15-30 ng/mL) for 2-3 weeks would dramatically cause cell morphology change . Compare to control cell with round and flat epithelial like morphology, low dose Alimta treated cells showed mesenchymal to amoeboid phenotype. Further examination of epithelial to mesenchymal transition (EMT) markers showed the expression level of N-cadherin, matrix metalloproteinase 1 (MMP-1) and matrix metalloproteinase 2 (MMP-2) increased. Associated with morphology and EMT marker changed, cell migration and invasion ability of those Alimta treated cells were 3 folds higher than control cells. Besides, evaluated drug sensitivity by sulforhodamine B (SRB) method showed that those alimta treated cells were more resistant to gefitinib. These prominent events provoked our interesting to investigate the mechanism involving in the oncogenic effect induced by low dose Alimta treatment. While examing EMT-related transcription factors, both Slug and SOX-9 expression increased significantly. These evidences indicated that the folate metabolism defect induced metastasis could through the SOX-9 and Slug mechanism. Citation Format: Chun-Te Ho, Tsan-Zon Liu, Yu-Ting Chou, Shih-Hsin Hsiao, Jun-Jen Liu. Folate metabolism defect induce invasion and Gefinitib resistance in lung cancer. [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 4970. doi:10.1158/1538-7445.AM2013-4970 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
A3.9 IL-17RA Signalling is Essential for Collagen Induced Arthritis Development
Authors: Odilia BJ Corneth, Adriana MC Mus, Patrick S Asmawidjaja, Maarten D Brem, Franka Luk, Wendy Dankers, Rudi W Hendriks, Erik Lubberts
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Introduction</h3> IL-17A plays an important role in collagen-induced arthritis (CIA). It signals through the IL-17 receptor (IL-17R) A and C heterodimer. The IL-17RA appears to be a common receptor subunit for several IL-17 cytokine family members, including IL-17A, IL-17C and IL-17F. Lack of IL-17RA signalling may therefore have a broader effect than lack of IL-17A alone. We therefore aim to determine the role of IL-17RA signalling in arthritis. <h3>Methods</h3> Disease incidence and severity were scored in wild type (positive control), IL-17RA deficient and IL-23p19 deficient (negative control) mice in CIA. T helper cell profiles and humoral immune responses were analysed by flow cytometry and immuno-histo-chemistry. Serum auto-reactive IgG antibodies were measured by ELISA. Pathogenicity of T cells and total splenocytes was determined in a functional assay in vitro. <h3>Results</h3> As expected, wild type mice developed CIA from day 21 after the first immunisation. IL-23p19 deficient mice did not develop arthritis. Interestingly, IL-17RA deficient mice were completely protected against CIA, even after a third immunisation. This is in contrast to IL-17A deficient mice, of which 20% is still susceptible to CIA. T cells in IL-17RA deficient mice display a Th2-like phenotype in CIA with higher proportions of IL-4 producing CD4 T cells. This population is distinct from IL-17A producing T cells. The shift in T cell phenotype induces a less inflammatory B cell response with fewer plasma cells in the spleen and lower pathogenic IgG2a antibody production in favour of IgG1 production. In a functional assay, both isolated CD4+ T cells and total splenocytes of IL-17RA deficient mice were less capable of inducing pro-inflammatory IL-6 production by normal, IL-17RA expressing synovial fibroblasts in CIA in vitro. <h3>Conclusions</h3> Here we show that lack of IL-17RA signalling prevents auto-immune inflammation of the joint. In addition, T helper cells shift to a Th2 like phenotype characterised by IL-4 production. T cells and splenocytes of these mice are less pathogenic, leading to lower pathogenic IgG2a antibody levels in serum. This is in contrast with IL-17A deficient mice and suggests that other factors involved in CD4+ T cell differentiation and pathogenicity can signal through the IL-17RA.
FRI0252 Tocilizumab improves arterial stiffness in rheumatoid arthritis irrespective of its disease activity control effects
Authors: K. Kume, K. Amano, S. Yamada, T. Kanazawa, H. Komori, K. Hatta, K. Amano
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tocilizumab(TCZ) improves artrerial stiffeness. Sometime TCZ improves artrerial stiffness even at higher level of disease activity. There is no evidence that association of disease activity and arterial stiffness after TCZ treatment has not shown. <h3>Objectives</h3> To evaluate TCZ therapy improves arterial stiffness beyond its effects of disease activity. <h3>Methods</h3> We used only high disease activity data(simplified disease activity index(SDAI) at baseline from our several clinical trial data that were treated by TCZ therapy(n= 87). All 87 RA patients had no previous history of cardiovascular disease or steroid treatment. Patients were divided into low, moderate and high disease activity at one year of TCZ treatment by SDAI(low disease activity(LDA), moderate disease activity(MDA), and high disease activity(HDA)). Arterial stiffness was assessed by cardio-ankle vascular index(CAVI; CAVI is modified Pulse Wave Velocity), and aortic augmentation index normalized to a fixed heart rate of 75 beats per minute (AIx@75). Improvement of CAVI and AIx@75 were compared between LDA, MDA, and HAD at one year of treatment(Kruskal.Wallis). <h3>Results</h3> Charatceristics at baseline were similar among the groups(LDA, MDA, and HDA group at one year). Improvement of CAVI was -0.85±0.16, -0.89±0.22, and, -0.84±0.31, respectively(in LDA, MDA and HDA). Improvement of AIx@75 was -2.38±0.35, --1.85±0.32, and, -2.58±0.58, respectively(in LDA, MDA and HAD). Improvement of CAVI and AIx@75 were not correlated disease activity at one year of TCZ treatment(CAVI: p=0.87, AIx@75: p=0.78). <h3>Conclusions</h3> TCZ improves arterial stiffness independently of its effects on disease activity, since even in HDA is halted. This indicates that IL-6 inhibition therapy conveys profound anti- arterial stiffness effects and dissociates the link between disease activity and arterial damage. <b>References:</b> Kume K, Amano K, Yamada S, Hatta K, Ohta H, Kuwaba N. et al. Tocilizumab monotherapy reduces arterial stiffness as effectively as etanercept or adalimumab monotherapy in rheumatoid arthritis: an open-label randomized controlled trial. J Rheumatol. 2011 Oct;38(10):2169-71. <b>Disclosure of Interest</b>: None Declared
Abstract 734: Frequency and type of epidermal growth factor receptor mutation in basaloid squamous cell carcinoma of the upper aerodigestive tract
Authors: Kyung-Ja Cho, Sung-Min Chun, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Sung Bae Kim
Journal: Cancer Research (2012)

Abstract Recent reports on nonsmall cell lung cancer (NSCLC) that epidermal growth factor receptor (EGFR) mutation status predicts response to EGFR-tyrosine kinase inhibitor (TKI) treatment signifies the importance of molecular footprint of EGFR. The mass array system has emerged as a more sensitive and economical method of mutation typing than direct sequencing. Basaloid squamous cell carcinoma (BSCC) is an aggressive variant of squamous cell carcinoma of the upper aerodigestive tract. We observed unexceptional EGFR expression in this type of malignancy by immunohistochemistry, and 23 cases (8 hypopharynx, 7 esophagus, 3 oropharynx, 2 oral cavity, 1 larynx, 1 paranasal sinus, 1 external auditory canal) with diffuse EGFR positivity were subjected to mutation analysis. Briefly, genome DNA from formalin-fixed paraffin embedded blocks were run through ASAN Panel, which addresses 74 somatic mutations including 38 point and 36 indel mutations for EGFR, KRAS, BRAF, and PIK3CA genes. Amplified PCR products in 8 separated multiplex fashion were treated with shrimp alkaline phosphatase, and followed by single base extension reaction using iPLEX-Pro kit from Sequenom with extension primers that hybridize immediately adjacent to the mutations. After incubation with resin for removing salt adductive, products were transferred to SpectroCHIPII for analysis using MALDI-ToF. Eight cases (35%) of BSCC were found to have substitution mutations or deletions in EGFR exon 18∼21, including both sensitive (L858R, del19) and resistant types (T790M) to EGFR-TKI. Two cases showed KRAS or PIK3CA point mutation. The results confirmed the mismatch between EGFR expression and mutation status in BSCC, and the presence of various mutations like NSCLC. Tailoring EGFR-TKI therapy for a subset of BSCC patients is in prospect. 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 734. doi:1538-7445.AM2012-734
Acute Leukemia in Identical Twins: Search for Viral and Leukemia-Associated Antigens&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: P H Levine, R B Herberman, E B Rosenberg, P D McClure, A Roland, R J Pienta, R C Ting
Journal: JNCI Journal of the National Cancer Institute (1972)

Journal Article Acute Leukemia in Identical Twins: Search for Viral and Leukemia-Associated Antigens Get access Paul H. Levine, Paul H. Levine Search for other works by this author on: Oxford Academic PubMed Google Scholar Ronald B. Herberman, Ronald B. Herberman Search for other works by this author on: Oxford Academic PubMed Google Scholar Eugene B. Rosenberg, Eugene B. Rosenberg Search for other works by this author on: Oxford Academic PubMed Google Scholar Peter D. McClure, Peter D. McClure Search for other works by this author on: Oxford Academic PubMed Google Scholar Augustine Roland, Augustine Roland Search for other works by this author on: Oxford Academic PubMed Google Scholar Roman J. Pienta, Roman J. Pienta Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert C. Y. Ting Robert C. Y. Ting Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 49, Issue 4, October 1972, Pages 943–952, https://doi.org/10.1093/jnci/49.4.943 Published: 01 October 1972 Article history Received: 16 January 1972 Accepted: 18 May 1972 Published: 01 October 1972
Chronic Mastoid Sinusitis Mimicking Metastatic Disease Demonstrated by Tc-99m HMDP Bone Scintigraphy
Authors: TSUNEO HIRANO, HIDENORI OTAKE, KAZUHIDE ICHIKAWA, YOSHIMICHI OHMORI, KAZUYOSHI KUNITOMO
Journal: Clinical Nuclear Medicine (1998)

A 46-year-old woman who had a middle ear infection 15 years earlier underwent Tc-99m HMDP bone scintigraphy as a follow-up for breast carcinoma. Intense uptake was seen in the right temporal calvarium on planar and SPECT images. Cranial CT showed diffuse sclerotic change in the hypoplastic right mastoid air cells, probably related to the prior inflammatory change.
IS RETINAL LAYER THICKNESS RELATED TO CORONARY ATHEROSCLEROSIS? A STUDY WITH RETINAL OPTICAL COHERENCE TOMOGRAPHY AND CORONARY INTRAVASCULAR ULTRASOUND-VH
Authors: Tomas Kovarnik, Zhi Chen, Andreas Wahle, Hana Skalicka, Ales Kral, Kyungmoo Lee, Ling Zhang, Martin Meliska, John Lopez, Milan Sonka, Ales Linhart
Journal: Journal of the American College of Cardiology (2016)
Cerebellar arm ataxia: Theories still have a lot to explain
Authors: J. Hore
Journal: Behavioral and Brain Sciences (1996)

Theories of cerebellar arm function should be able to explain the now well-characterized disorders that occur during cerebellar dysfunction in fast arm movements made at single joints. Contrary to claims in Smith's target article, cocontraction is not one of these disorders. Although loss of the joint stiffness function proposed by Smith is consistent with some findings, it does not explain all of these disorders, and therefore gives only a limited view of cerebellar function, [SMITH]
Abstract 4297: Morphology of MCF-7 colonies formed in agarose cell culture
Authors: Amy L. Aulthouse, Elizabeth Di Nino, David H. Kinder
Journal: Cancer Research (2011)

Abstract Previously, we demonstrated that the MCF-7 cell line grows in a permissive 3-D agarose culture (Kinder and Aulthouse, Cancer Letters., 2004, 205(1), 49-53). Single cells form colonies over time; thus, mitotic activity can be monitored in response to various agents. We studied the morphology of the colonies that formed following growth from single cells at 3 time points: 1.5, 2, 2.5 weeks. The MCF-7 cells grew into clusters (solid) and hollow tube-like structures. These structures were confirmed by H&amp;E stained serial sections of paraffin embedded cultures. H&amp;E staining also revealed abundant mitotic figures. Because calcium foci are common in breast cancers, we also evaluated the cultures for calcium expression using the von Kossa reaction. Placenta was used as a control. At all time points, calcium was detected, but no particular pattern was noted in the calcium distribution between the clusters and the hollow tube-like structures. With morphology and calcium expression described, we further examined cell growth inhibition and cytotoxicity of estradiol and tamoxifen on the MCF-7 cells. Added estradiol enhanced the growth of the cells, while tamoxifen was cytostatic at concentrations below 1.3 × 10-4 nM. At high tamoxifen concentrations (&amp;gt;2 × 10-4 nM) cytotoxicity was noted. This was likely due to sigma-2 receptor binding rather than estrogen receptor blocking. Combination of estradiol with tamoxifen had a more pronounced effect on the cytotoxicity caused by tamoxifen. These morphological and mechanistic findings support the use of this model for studying the MCF-7 cell line in agarose culture. 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 4297. doi:10.1158/1538-7445.AM2011-4297
Secondary Biosynthetic Defects in Women with Late-Onset Congenital Adrenal Hyperplasia
Authors: Talia Eldar-Geva, Arye Hurwitz, Paul Vecsei, Zvi Palti, Ariel Milwidsky, Ariel Rösler
Journal: New England Journal of Medicine (1990)

Late-onset (non-classic) congenital adrenal hyperplasia is a cause of hirsutism, menstrual disorders, and infertility, but its frequency and the patterns of abnormalities in adrenal hormone secretion are not well understood. We investigated the frequency and ethnic distribution of nonclassic congenital adrenal hyperplasia due to deficiencies of 3 beta-hydroxy-delta 5-steroid dehydrogenase, 21-hydroxylase, or 11 beta-hydroxylase among 170 Israeli Jewish women with these clinical problems. All enzyme defects were identified by comparing the patients' hormonal responses to a 0.25-mg intravenous bolus dose of alpha 1-24-ACTH with those of 26 age-matched normal women.Twenty women (12 percent) had 3 beta-hydroxy-delta 5-steroid dehydrogenase deficiency, 18 (10 percent) 21-hydroxylase deficiency (14 homozygous), and 14 (8 percent) 11 beta-hydroxylase deficiency. All the homozygous women with 21-hydroxylase deficiency also had evidence of a partial deficiency in 11 beta-hydroxylase activity. Similarly, most of the women with 11 beta-hydroxylase deficiency also had evidence of a deficiency in 3 beta-hydroxy-delta 5-steroid dehydrogenase. Among the 118 women with no adrenal biosynthetic defect, 38 had high plasma androgen concentrations, and 80 had normal concentrations.About one third of Israeli Jewish women with hirsutism, menstrual disorders, or unexplained infertility had nonclassic congenital adrenal hyperplasia. Secondary adrenal biosynthetic defects were frequent in these women and were probably caused by intra-adrenal androgen excess rather than by dual inherited enzymatic deficiencies.
Medicare Part D — The Product of a Broken Process
Authors: Louise M. Slaughter
Journal: New England Journal of Medicine (2006)

Most Americans agree that affordable drug coverage under Medicare has been needed for some time. But instead of a solution to a growing problem, Congress gave the country a prescription-drug plan that achieves few of its original goals. The current problems with Medicare Part D are largely the direct result of the undemocratic way in which the plan was authored and passed. The final legislation, heavily influenced by drug-company and health insurance lobbyists, focused mainly on the needs of those industries instead of those of the seniors it should serve.The political process used to pass Part D was the . . .