tbuckley/cabot-search huggingface dataset:
Abstract 443: Expression of the RECK tumor and metastasis suppressor gene in human breast cancer: a poor prognosis marker
Authors: Luciana R. Gomes, Andre Fujita, Fernando A. Soares, Leticia Labriola, Mari C. Sogayar
Journal: Cancer Research (2012)

Abstract Metastasis is the main cause of mortality in breast cancer human patients. The organized breakdown of the extracellular matrix (ECM) compounds by matrix metalloproteinases (MMPs) is the key event in this metastatic process. Consistent with their role in tumor progression, high levels of several MMP family members have been shown to be correlated with poor prognosis. The MMP activities are tightly regulated by their inhibitors, namely: the metalloproteinases tissue inhibitors (TIMPs) and the membrane-associated inhibitor (RECK - Reversion-inducing Cysteine-rich protein with Kazal motifs). Due to RECK's ability to down modulate MMPs (MMP-2, 9 and 14), it is described as an important inhibitor of invasion and metastasis in several types of cancer. In order to investigate possible correlations between the RECK expression profile and clinical-pathological data in a breast cancer model, we evaluated the RECK protein in 1,040 tissue samples from invasive breast tumors using Tissue Microarray Assays (TMA). Associations between RECK expression and different clinical-pathological parameters and other biomarkers were evaluated using the Chi-square test. RECK immunoreactivity was significantly associated with higher SBR grade (p&amp;lt;0.05) and TNM stage (p=0.002). Moreover, higher RECK expression levels were correlated with p53 (p&amp;lt;0.001), her-2 (p=0.011), CK5,6 (p&amp;lt;0.001) and egfr (p&amp;lt;0.001) positivity. We also analyzed the relationship between RECK expression and the patient outcome, using Kaplan-Meier curves, demonstrating that patients with RECK positive tumors display significantly shorter disease free survival time (p=0.031) than those with RECK negative tumors. Furthermore, RECK expression was positively correlated with short disease free survival in five-years in patients diagnosed with tumors: low SBR grade (p=0.03), her-2 negative (p&amp;lt;0.05) and luminal markers (CK8/CK18) positive (p=0.02 and p=0.003, respectively). In addition, RECK was a predictor of poor prognosis for post-menopause (p=0.011) and patients older than 50 years (p=0.05). All together, our results indicate that higher RECK expression is associated with poor prognosis variables, being a predictor of shorter disease-free survival in five years. Moreover, we verified that RECK is a biomarker of poor prognosis mainly for patients diagnosed with less aggressive breast tumor. Therefore, in contrast to other tumor types, our results indicate that RECK is related to a more aggressive phenotype. Support: FAPESP, CNPq, FINEP, CAPES, BNDES 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 443. doi:1538-7445.AM2012-443
Abstract 2930: Novel colorectal cancer loci in multiplex-proficient mismatch repair families
Authors: Julie M. Cunningham, Mine Cicek, Fridley Brooke, Daniel Serie, William Bamlet, Brenda Diergaarde, Robert Haile, Loic Le Marchand, Theodore Kontriris, Ban Younghusband, Steven Gallinger, Polly Newcomb, John Hopper, Mark Jenkins, Graham Casey, Frederick Schumacher, Zhu Chen, Allyson Templeton, Ingrid Winship, Roger Green, Macrae Finlay, Susan Parry, Graeme Young, Joanne Young, Daniel Buchanan, Duncan Thomas, D. Timothy Bishop, Noralane Lindor, Stephen Thibodeau, John Potter, Ellen Goode
Journal: Cancer Research (2012)

Abstract A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no tumors with loss of expression of MMR proteins; no microsatellite instability (MSI)-high tumors, and no evidence of linkage to MMR genes). This represents the largest linkage analysis of proficient MMR (pMMR) familial CRC to date. Families were ascertained via the NCI-supported Colon Cancer Family Registry multi-site (Colon CFR) consortium, the City of Hope, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family, range 2-10 with an average of 2.2 affected and 2.8 unaffected individuals) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed, accounting for heterogeneity, in four chromosomal regions. The greatest lod scores were at 4q21.1 among families with mean age of diagnosis less than 50 years (dominant HLOD=4.51, α=0.84, 145.40 cM, rs10518142) and at 12q24.32 among all families (dominant HLOD=3.60, α=0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD=3.07, α=0.29; dominant HLOD=3.03, α=0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD=3.02, α=0.51, 132.52 cM, rs1319036). These linkage regions comprise previously unreported loci, supporting the hypothesis that novel loci contribute to CRC in familial pMMR cases. These loci are also largely distinct from those identified in case-control GWAS. To follow up on these findings, a custom Agilent Sure Select Target Enrichment panel has been designed for genes in three of these regions, in order to sequence probands using an Illumina HiSeq 2000. This study demonstrates the utility of family-based data and provides evidence for additional alleles for familial CRC. 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 2930. doi:1538-7445.AM2012-2930
Studies of Liver Glycogenoses, with Particular Reference to the Metabolism of Intravenously Administered Glycerol
Authors: Boris Senior, Liliane Loridan
Journal: New England Journal of Medicine (1968)

To investigate the pathophysiology of glycogenoses of the liver, glycerol, an endogenous precursor of glucose, was administered intravenously to eight patients and to 22 control subjects. Its disposal rate and effect on the levels of glucose and of lactate were measured. In all patients, particularly those lacking glucose-6-phosphatase, the disposal rate of glycerol was more rapid than in control subjects. Elevation of glucose levels was less than normal in the patients lacking glucose-6-phosphatase, and more than normal but with distinctive patterns in a patient deficient in amylo-1,6-glucosidase, and in two considered to lack a component of phosphorylase. Lactate levels were elevated only in patients lacking glucose-6-phosphatase. A single patient responded similarly to those lacking glucose-6-phosphatase but had normal enzyme activity in the liver on in vitro assay. This condition is proposed to be a variant of von Gierke's disease in which glucose-6-phosphatase activity, although present in vitro, is inactive in vivo.
Abstract 3757: CR8, a novel CDK inhibitor, enhances vandetanib activity in a human medullary thyroid carcinoma model
Authors: Sophie Broutin, Morgane Hervé-Bazin, Frédéric Commo, Nassima Oumata, Laurent Meijer, Corinne Dupuy, Martin Schlumberger, Jean-Michel Bidart
Journal: Cancer Research (2012)

Abstract Introduction: CR8 (ManRos Therapeutics) is a novel inhibitor of cyclin-dependent kinases (CDKs) that selectively targets CDK1/2/3/5/7/9. CDK inhibitors have already shown potent antitumoral activity. Recently, vandetanib (Astra Zeneca), a tyrosine-kinase inhibitor, was approved in the U.S. for the treatment of adult patients with metastatic Medullary Thyroid Carcinoma (MTC). The absence of complete tumor responses justifies the development of new therapeutic options. The aim of this study was to investigate the preclinical activity of CR8 alone and in combination with vandetanib in a MTC model. Materials and Methods: The human MTC TT cell line, bearing a RETC634W activating mutation, was cultured in the absence or the presence of CR8 (10-10 000 nM) and/or vandetanib over 6 days. Cell proliferation was assessed by WST-1 assay. Activation of RET, PP1α and oncogenic pathways (PI3K/AKT, MEK/p44-42) was analyzed by western-immunoblotting. Calcitonin secretion in cell culture media was measured by ELISA. Results: Both CR8 and vandetanib when used alone strongly inhibit TT cell proliferation at day 3 of treatment. Addition of CR8 (10 nM) enhances the antiproliferative activity of low vandetanib concentrations. As expected, vandetanib alone inhibits RET, MAPK and AKT phosphorylation and CR8 inhibits PP1α. Interestingly, CR8 alone induces activation of RET, MAPK and AKT phosphorylation, and the addition of vandetanib (&amp;gt;100 nM) inhibits RET signalling pathways. At day 3 of treatment, vandetanib (&amp;gt;100 nM) and CR8 (100 nM) reduced and induced calcitonin secretion, respectively. Conclusion: CR8 displays an antiproliferative effect on TT cells and enhances the antiproliferative activity of vandetanib. CR8 acts by inhibiting PP1α and, surprisingly, induces an activation of RET and stimulates calcitonin production. These results suggest that the combination of vandetanib with CDKs inhibitors such as CR8 may be of value to improve therapeutic response. 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 3757. doi:1538-7445.AM2012-3757
SAT0249 Tocilizumab in the Treatment of Patients with Rheumatoid Arthritis in REAL Clinical Practice: Results of TRUST Study: Table 1.
Authors: R. Gerli, A. Afeltra, G. Bagnato, G. Carlino, R. Foti, A. Mazzone, G. Minisola, N. Pappone, R. Russo, A. Semeraro
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Tocilizumab (TCZ) is an interleukin-6 receptor inhibitor for treatment of patients (pts) with moderate to severe rheumatoid arthritis (RA) and inadequate response (IR) to disease modifying anti-rheumatic drugs (DMARDs) or anti-Tumor Necrosis Factor (anti-TNF) agents. <h3>Objectives</h3> Describe the efficacy and safety of TCZ in pts with RA in Italian clinical practice. Primary endpoint: proportion of pts with remission or low disease activity (LDA) after 6 months of TCZ treatment. <h3>Methods</h3> TRUST is a multicenter, retrospective-prospective, observational study in pts with RA who had started treatment with TCZ in the 6 months prior to center opening and were still on treatment at the beginning of the study (retrospective phase); pts were then followed up to a maximum of 12 months after the first TCZ infusion (prospective phase). <h3>Results</h3> A total of 322 RA pts were enrolled in 59 Italian centers (mean age: 55.8 years; mean disease duration: 120.5 months; baseline DAS28: 5.3). After 6 months of TCZ treatment, the proportion of pts (57.52%, N=130, p-value&lt;0.0237) achieving LDA (DAS28 ≤3.2) and disease remission (DAS28 ≤2.6; 38.05%, N=86, p-value=0.0003) out of 226 pts with available DAS28 were statistically significant vs baseline. A considerable proportion of pts (32.6%, N=105) was treated in monotherapy with TCZ; clinical benefits are shown in table 1. No statistically significant differences were found between the two subpopulations of pts: DMARD-IR or TNF-IR in the mean DAS28 and HAQ score from baseline to any post-baseline time point, while a statistically significant difference was found in the mean VAS Fatigue score (48.4 vs. 34.7; p=0.0025) after 6 months of TCZ treatment. 62 pts (19.2%) prematurely discontinued TCZ, 24 for safety reasons. Drug-related adverse events were reported in 28.6% (N=92) of pts (mostly hypercholesterolemia and leucopenia) and serious adverse events in 3.4% (N=11) of patients. Adverse events of special interest were reported in 60 pts (mostly infections). <h3>Conclusions</h3> This study confirms the efficacy of TCZ in pts with RA, as it shows a high proportion of patients achieving a low disease activity (57.52%) or disease remission (38.05%) after 6 months of treatment. The clinical benefits of TCZ are also shown in patients treated with TCZ as monotherapy, where DAS28, VAS Fatigue and HAQ scores markedly improved. The low incidence of drug-related adverse events (28.6%) and serious adverse events (3.4%) confirms also the good safety profile of TCZ. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5029
Spinal Cord Stimulation in Patients with Chronic Reflex Sympathetic Dystrophy
Authors: Marius A. Kemler, Gerard A.M. Barendse, Maarten van Kleef, Henrica C.W. de Vet, Coen P.M. Rijks, Carina A. Furnée, Frans A.J.M. van den Wildenberg
Journal: New England Journal of Medicine (2000)

Chronic reflex sympathetic dystrophy (also called the complex regional pain syndrome) is a painful, disabling disorder for which there is no proven treatment. In observational studies, spinal cord stimulation has reduced the pain associated with the disorder.
THU0467-HPR A standardized educational program directed to patients for self-care promotion can be equally effective in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ankylosing spondylitis (AS)
Authors: L. Cano-García, R. Navas-Fernández, F.G. Jiménez-Nuñez, I. Ureña, S. Manrique, C.M. Romero-Barco, V. Rodríguez-García, L. Nieves-Martín, M. Ά. Belmonte-Lόpez, V. Coret, M.C. Ordόñez, M.V. Irigoyen, A. Fernández-Nebro
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To evaluate the results of a standardized educational intervention to improve the quality of life related to health (HRQL), physical function, adherence and pain perception in 3 diagnostic groups (RA, SLE, AS). <h3>Methods</h3> <i>Design:</i> Uncontrolled open intervention. Patients: 30 RA (ACR criteria), 30 AS (ASAS criteria) and 23 SLE (ACR criteria) followed in the Rheumatology Service, HRUCH. <i>Intervention:</i> Training Group activity was provided by a nurse, an occupational therapist and a physiotherapist. The main topics were: (1) what is the AR/AE/SLE? (2) The treatment; (3) Promoting healthy behaviours and joint protection; (4) non-pharmacological management of pain; (5) Physical activity; and (6) Technical aids for daily living. <i>Outcomes and variables:</i> HRQL was assessed with EQ-5D and SF-36, the perception of pain and patient disease assessment with a VAS (0-100), physical function by HAQ for RA and SLE, HAQ-AS for AS, the adherence by Moriski-Green test, the chronic pain with chronic pain coping questionnaire (CAD-R). All variables ere collected before educational activity and after 3 months. <i>Statistical analysis:</i> Comparison between diagnostic groups of quantitative variables was performed by ANOVA one factor. <h3>Results</h3> A total of 83 patients were studied: 30 with RA (83.3% women), 23 with SLE (100% women) and 30 with AS (33.3% women). The intervention improved the HRQL expressed as EQ-5D (p&lt;0.001), EQ-5D health VAS (p&lt;0.001) and mental component SF-36 (p=0.006). There was improvement in VAS pain (p=0.012), VAS disease (p=0.028) and CAD-R (p&lt;0.001) also in all patients. Although there were no differences in CAD-R of diagnostic subgroups, a difference in VAS pain at baseline (p=0.019) and after 3 months (p=0.038) between AS and RA (p=0.044) was detected (in favour of AS). Patients with HAQ-AS post-intervention improved more than HAQ of SLE-patients (p&lt;0.005). No differences for diagnosis were detected in Moriski-Green test. <h3>Conclusions</h3> This standardized educational program directed to patients with AS, RA and SLE for self-care promotion produce an improvement quite homogeneous in all patients independent their diagnosis. <h3>Disclosure of Interest</h3> None Declared
Mesenteric Abscess in Crohn's Disease
Authors: Tyson J Teeples, James H Tabibian
Journal: New England Journal of Medicine (2013)

A 44-year-old woman with a history of Crohn's disease presented with a 1-week history of progressive abdominal distention, nausea, and feculent vomiting and reported having lost 13.6 kg during the preceding 6 months. She had undergone ileocecostomy 20 years earlier.
Differentiation Between Early and Late Membrane Antigen on Human Lymphoblastoid Cell Lines Infected With Epstein-Barr Virus. I. Immunofluorescence2
Authors: I. Ernberg, G. Klein, F.M. Kourilsky, D. Silvestre
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Differentiation Between Early and Late Membrane Antigen on Human Lymphoblastoid Cell Lines Infected With Epstein-Barr Virus. I. Immunofluorescence Get access I. Ernberg, I. Ernberg 3Department of Tumor Biology, Karolinska Institutet, S-10401 Stockholm 60, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Klein, G. Klein 3Department of Tumor Biology, Karolinska Institutet, S-10401 Stockholm 60, Sweden. Search for other works by this author on: Oxford Academic PubMed Google Scholar F.M. Kourilsky, F.M. Kourilsky 4Laboratoire d'lmmunologie des Tumeurs, Institut de Recherches sur les Leucernies, Hopital Saint Louis, 75010 Paris, France. Search for other works by this author on: Oxford Academic PubMed Google Scholar D. Silvestre D. Silvestre 4Laboratoire d'lmmunologie des Tumeurs, Institut de Recherches sur les Leucernies, Hopital Saint Louis, 75010 Paris, France. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 53, Issue 1, July 1974, Pages 61–65, https://doi.org/10.1093/jnci/53.1.61 Published: 01 July 1974 Article history Received: 23 December 1973 Accepted: 10 April 1974 Published: 01 July 1974
Pseudoprogression in patients with glioblastoma: clinical relevance despite low incidence
Authors: A. Radbruch, J. Fladt, P. Kickingereder, B. Wiestler, M. Nowosielski, P. Baumer, H.-P. Schlemmer, A. Wick, S. Heiland, W. Wick, M. Bendszus
Journal: Neuro-Oncology (2014)

According to the Response Assessment in Neuro-Oncology criteria, new enhancement within the radiation field on contrast enhanced T1-weighted images within 12 weeks after completion of radiotherapy should not qualify for progressive disease, since up to 50% of these cases may be pseudoprogression (PsP). To validate this concept, we assessed incidence and overall survival (OS) of patients with suspected and confirmed PsP dependent on different time intervals and definitions of PsP. Patients with newly diagnosed glioblastoma and an enhancement increase of at least 25% after completion of standard radiochemotherapy at month 1, 4, 7, or 10 were eligible. Based on the development of the enhancement in follow-up examinations, patients were categorized as either PsP (subgrouped as complete resolution/decrease >50% and decrease <50%/stable) or true progression. Out of 548 patients, 79 fulfilled the inclusion criteria. Of these 79 patients, 9 (11.4%) showed PsP (6/45 patients at 1 month, 2/17 at 4 months, 1/9 at 7 months, and 0/8 at 10 months). Complete resolution of the enhancement was found in 1, decrease >50% in 3, decrease <50% in 2, and stable enhancement in 3 patients with PsP. Patients with PsP showed a significantly longer OS (P < .012). No difference in OS was found among PsP subgroups. This series challenges the current concept of PsP. Even though we could confirm a prolonged OS of patients with PsP, the incidence of PsP was lower than reported previously and extended beyond 12 weeks.
Abstract 1964: Genetic instability and mammary tumor formation in mice carrying mammary-specific disruption of Chk1
Authors: Yuing Li, Thomas Fischler, Xiaoling Xu, Rui-Hong Wang, Hyun-Seok Kim, Kundan Sengupta, Athanassios Vassilopoulos, Tyler Lahusen, Qinghua Liu, Steve Elledge, Thomas Ried, Chuxia Deng
Journal: Cancer Research (2010)

Abstract Chk1 is a key element in the DNA damage response pathway that is required for maintaining genomic stability. To study the potential role of Chk1 in mammary tumorigenesis, we disrupted it using a Cre/loxP system. We showed that although Chk1 haploinsufficiency caused abnormal development of the mammary gland, it was not sufficient to induce tumorigenesis. Simultaneous deletion of one copy of p53 failed to rescue the developmental defects; however, it synergistically induced mammary tumor formation in Chk1+/-;MMTV-Cre animals with a median time to tumor latency of about 10 months. Chk1 deficiency caused a preponderance of abnormalities, including prolongation, multipolarity, misalignment, mitotic catastrophe and loss of spindle checkpoint that is accompanied by reduced expression of several cell cycle regulators, including Mad2. On the other hand, we also showed that Chk1 deficiency inhibited mammary tumor formation in mice carrying a homozygous deletion of p53, uncovering a complex relationship between Chk1 and p53. Furthermore, inhibition of Chk1 with a specific inhibitor, SB-218078, or acute deletion of Chk1 using shRNA killed mammary tumor cells effectively. These data demonstrate that Chk1 is critical for maintaining genome integrity and serves as a double-edged sword for cancer: while its inhibition kills cancer cells, it also triggers tumorigenesis when avorable mutations are accumulated for cell growth. 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 1964.