tbuckley/cabot-search huggingface dataset:
Fibrin and Fibrinogen-Related Antigens in Patients with Stable and Unstable Coronary Artery Disease
Authors: J B Kruskal, P J Commerford, J J Franks, R E Kirsch
Journal: New England Journal of Medicine (1987)

Coronary-artery thrombosis may be important in the pathogenesis of unstable angina at rest. To study this possibility, we measured the serum concentrations of fibrin-related antigen, D dimer (the principal breakdown fragment of fibrin), and fibrin monomer (an intermediate product of fibrin formation) in the serum of five groups of subjects. These included 10 healthy controls, 10 controls with noncardiac pain, and three groups of 10 patients each with chronic stable angina, unstable angina at rest, or acute myocardial infarction. The concentration of fibrin-related antigen (normal range, 48 to 184 ng per milliliter) was normal in the control patients with noncardiac pain (63 to 202 ng per milliliter) and in patients with chronic stable angina (95 to 186), but it was increased in patients with unstable angina (401 to 2507) or acute myocardial infarction (470 to 1930) (P less than 0.001). D dimer concentrations in patients with unstable angina (178.3 to 310.6 ng per milliliter) or acute myocardial infarction (103.9 to 321.6) were higher than those in patients with chronic stable angina (28.6 to 52.1), in controls with noncardiac pain (44.7 to 53.1), and in healthy controls (40.4 to 50.3) (P less than 0.001). Concentrations of fibrin monomer were highest in patients with acute myocardial infarction (247.5 to 571.3 ng per milliliter) (P less than 0.001), intermediate in those with unstable angina (54.7 to 241.7) (P less than 0.001), and normal (normal range, 14.5 to 19.8 ng per milliliter) in controls with noncardiac pain (12.0 to 18.4). and patients with chronic stable angina (10.7 to 17.6). These findings suggest the presence of an active thrombotic process in patients with unstable angina at rest or acute myocardial infarction. The data do not prove that the coronary arteries were the site of the thrombotic process, but the observations are consistent with the hypothesis that thrombus formation may have an important role in the pathogenesis of these conditions.
Detection of Borrelia burgdorferi DNA by Polymerase Chain Reaction in Synovial Fluid from Patients with Lyme Arthritis
Authors: James J. Nocton, Frank Dressler, Barbara J. Rutledge, Paul N. Rys, David H. Persing, Allen C. Steere
Journal: New England Journal of Medicine (1994)

Borrelia burgdorferi is difficult to detect in synovial fluid, which limits our understanding of the pathogenesis of Lyme arthritis, particularly when arthritis persists despite antibiotic therapy.
Abstract 1818: Space-time analysis of racial disparities in advanced-stage prostate cancer incidence across Florida
Authors: Pierre Goovaerts, Hong Xiao
Journal: Cancer Research (2010)

Abstract Prostate cancer is the most frequently diagnosed non-skin cancer and the second leading cause of cancer-related death for American men. Florida ranks second behind California for both incidence and mortality from prostate cancer in 2008. With the wide spread use of prostate specific antigen (PSA) and digital rectal examination (DRE), a larger proportion of prostate cancer cases is now diagnosed at early stages. Yet, striking racial/ethnic differences in incidence and mortality still persist in the United States and Florida. Eliminating such disparities requires a better understanding of factors responsible for the geographic and ethnic differences in prostate cancer late stage incidence and mortality over time. Percentages of advanced-stage prostate cancer diagnosis were analyzed yearly from 1981 through 2005 for each county of Florida and three ethnic subgroups (white, black, Hispanic). All three ethnic groups experienced a 50% decline in the state-average proportion of late-stage diagnosis. This drop, which started in the early 1990s when PSA became widely available, was the most pronounced for Hispanics whose rates is now similar to white non-Hispanics; black non-Hispanics still have a 25% larger rate compared to the two other ethnic groups. Interestingly, the total number of diagnosed cases kept increasing for black and Hispanics, while it started declining slowly for white in the early 1990s. These temporal trends are however not uniform across Florida; cluster and boundary analysis revealed geographical disparities that were substantial for all ethnic groups before the mid 1990s. The gap among Florida counties is narrowing with time as the percentage of late-stage diagnosis is decreasing. One outlier is the Big Bend region of Florida where the decline in late-stage diagnosis has been the slowest in all Florida for both white and black males. While this paper focused on the geographic distribution of race-based disparities in advanced-stage prostate cancer diagnosis in Florida, the approach can be easily generalized to other states and cancer sites, with clear applications in (a) monitoring and surveillance of cancer incidence and mortality, (b) the generation of hypotheses for in depth individual studies of risk factors that are causal, or impact survival; and (c) establishing the rationale for targeted cancer control interventions, including consideration of health services needs, and resource allocation for screening and diagnostic testing. 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 1818.
Lymphoid Blast Crises of Chronic Myelogenous Leukemia Represent Stages in the Development of B-Cell Precursors
Authors: Ajay Bakhshi, Jun Minowada, Andrew Arnold, Jeffrey Cossman, Jane P. Jensen, Jacqueline Whang-Peng, Thomas A. Waldmann, Stanley J. Korsmeyer
Journal: New England Journal of Medicine (1983)

The origin and stage of differentiation of the blast-crisis cells in chronic myelogenous leukemia have remained uncertain. Because immunoglobulin heavy-chain and light-chain genes must undergo a DNA rearrangement during B-cell development but rarely do so in human non-B-cell lineages, we examined these genes in 18 episodes of chronic myelogenous leukemia. In eight of nine episodes of lymphoid blast crisis, heavy-chain genes were rearranged, and in three, rearrangements in light-chain genes were also present. In contrast, cells from chronic myeloid, myeloid blast, and erythroid-like phases retained germ-like immunoglobulin genes. The observed phenotypic markers and gene configurations revealed that most lymphoid blast crises represent stages of development of B-cell precursors. In two separate episodes of lymphoid crisis, cells from a single patient possessed identical heavy-chain but different light-chain-gene configurations. Thus, the precursor cells that monoclonally expand to produce a lymphoid crisis are capable of immunoglobulin-gene rearrangements and represent discrete steps in early B-cell maturation.
Unexpected Pregnancy Revealed on 18F-NaF PET/CT
Authors: Fuqiang Shao, Yue Chen, Zhanwen Huang, Liang Cai, Yin Zhang
Journal: Clinical Nuclear Medicine (2015)

A 48-year-old illiterate woman who is congenitally deaf and mute underwent 18F-NaF PET/CT study to evaluate bone metastases from newly diagnosed breast cancer. Unexpectedly, a fetus in early second trimester was noted on CT images. In addition, subtle 18F-NaF uptake by the fetus could also be observed.
Late Correlative Imaging Findings of Previous Acute Infective Spondylitis
Authors: E Vanninen, T Laitinen, K Partanen, H Tulla, A Herno, H Kröger
Journal: Clinical Nuclear Medicine (2000)

To evaluate late correlative imaging findings in relation to clinical outcome in persons with previous acute infective spondylitis, the authors performed bone and leukocyte scintigraphy (planar and SPECT imaging) and magnetic resonance imaging of the spine in nine patients (two men, seven women; mean age, 66 years; age range, 57 to 84 years) 3.1 years (range, 0.9 to 6.2 years) after the acute disease.All images were evaluated visually. The relevant uptake on SPECT images was also quantitated using an adjacent normal vertebral body as the reference area.Except for one patient, all other patients had increased uptake in the affected vertebra on bone scintigraphy [corrected]. In leukocyte scintigraphy, clearly decreased uptake was noted quantitatively in six of the seven patients who underwent SPECT. On the magnetic resonance and computed tomographic scans, the typical findings were destruction of intervertebral disks and compression deformities of vertebral bodies, but there was high interindividual variance of other findings, such as osteophytes, spondylolisthesis, increased vertebral fat content, and postoperative changes. These data show that nearly all patients with previously acute infective spondylitis have gross abnormal anatomic and functional imaging findings years after the acute disease, despite good clinical outcome [corrected].The utility of bone and leukocyte scans in the diagnosis of reactivated spondylitis is limited, and incidentally observed abnormal imaging findings in asymptomatic patients with known previous spondylitis should be interpreted with caution.
Abstract 5606: Gallium maltolate inhibits brain tumor volume and blood volume in xenograft model.
Authors: Kimberly R. Pechman, Andrew Lozen, Mona Al-Gizawiy, Kathleen Schmainda, Christopher R. Chitambar
Journal: Cancer Research (2013)

Abstract Purpose: There are limited treatment options for glioblastomas (GBM). Tumor cells have a high requirement for iron; the latter is taken up by cells through transferrin receptor-mediated endocytosis of transferrin-iron. These receptors are highly expressed on GBM cells, which makes them an attractive target for transferrin receptor-directed therapies. Gallium is a group IIIa metal that can function as an iron mimetic by avidly binding to transferrin and incorporating into cells through the transferrin receptor. No studies have been performed to determine the efficacy of gallium-based therapies in brain tumors. Consequently, the goal of this study was to evaluate gallium maltolate in the treatment of a U87 xenograft brain tumor model. Methods: Athymc rats bearing U87 human grade IV astrocytoma cells were studied. Gallium maltolate (50 mg/kg/day, n=5) or saline (n=3) was given intravenously. via an alzet mini pump in the jugular vein. Magnetic resonance imaging (MRI) was performed on days 8 and 18 on a Bruker 9.4 T scanner. Enhancing tumor volumes were determined from the post-contrast T1w images, in all slices showing enhancing tumor. The spin and gradient echo relaxation rate changes were then determined giving estimates of microvascular and total blood volume. ((CBVmicro≈R2=R2MION-R*pre-MION CBVTotal≈ R2* = R2*MION-R2*pre-MION). Results: Gallium maltolate inhibited tumor growth (377132%), as measured by enhancing tumor volume, compared to saline controls (863481%). Treatment shows decrease of CBV micro and CBVTotal compared to the controls. The ratio of R2* /R2, which is a measure of mean vessel diameter, increased in saline treated controls but remained unchanged for the gallium maltolate treated rats. To our knowledge this is the first study performed that uses physiologic MRI measurements to investigate the effects of gallium maltolate on brain tumor xenografts. The differences shown are not statistically significant a result likely due to the small sample sizes, which is being remedied by ongoing additional studies. For the imaging studies included here tissue markers of proliferation (Ki67), hypoxia (HIF1) transferrin receptors, and vascular density (vWF) are being analyzed to provide additional information regarding mechanism of action. In general these results demonstrate, for the first time, that the novel gallium maltolate treatment holds promise for the treatment of malignant brain tumors. Citation Format: Kimberly R. Pechman, Andrew Lozen, Mona Al-Gizawiy, Kathleen Schmainda, Christopher R. Chitambar. Gallium maltolate inhibits brain tumor volume and blood volume in xenograft model. [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 5606. doi:10.1158/1538-7445.AM2013-5606
OP0214 Investigation of rheumatoid arthritis genetic susceptibility markers in the early rheumatoid arthritis study (ERAS) provides further replication of the TRAF1/C5 association with radiological damage
Authors: S. Viatte, D. Plant, M. Lunt, B. Fu, B. Parker, J. Galloway, C. Solymossy, J. Worthington, D. Symmons, J. Dixey, A. Young, A. Barton
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> A rheumatoid arthritis (RA) susceptibility region between the TNF receptor-associated factor-1 and complement component 5 genes (<i>TRAF1/C5</i>) has previously been reported to associate with radiological damage in two studies. <h3>Objectives</h3> We aimed to test rheumatoid arthritis (RA) genetic susceptibility markers for association with a continuous measure of radiological damage over time using longitudinal modelling techniques in a discovery cohort of patients with inflammatory polyarthritis (IP). An independent inception cohort of UK IP patients was used as a replication cohort, and also combined together with the discovery cohort in order to increase sample size and power. <h3>Methods</h3> Sixty-seven RA susceptibility variants were genotyped in 474 patients from the Early Rheumatoid Arthritis Study (ERAS) using Sequenom MassArray technology. Correlation between genetic markers and Larsen score, as a time dependent trait, was assessed longitudinally using zero-inflated negative binomial regression to include repeat measurements in the same individual at different time points. Genetic markers associated with radiological damage in ERAS were tested using the same modelling techniques on previously published data from the Norfolk Arthritis Register (NOAR). Finally, the model was adapted to accommodate differences in disease progression between the two cohorts and a combined analysis was performed. <h3>Results</h3> rs2900180 at the <i>TRAF1/C5</i> locus was the single marker associated longitudinally with Larsen score in the ERAS cohort (p=0.02; time averaged effect size: 2.96 Larsen units) and in the NOAR cohort (p=0.04; effect size: 1.56). Analysis of individual time points in ERAS showed that TRAF1/C5 polymorphisms display their effect primarily on the extent of Larsen score early in the disease course (rs2900180, year 2: coef. 0.35 95%CI 0.04, 0.66, p=0.025; rs10760130, year 2: coef. 0.34 95%CI 0.03, 0.65, p=0.030). Combined longitudinal analysis of the two cohorts suggests further association of several loci with Larsen score (<i>KIF5A, PTPN22, AFF3, TAGAP</i>). <h3>Conclusions</h3> The genetic marker rs2900180 is associated with extent of erosions, as measured by the Larsen score, in the ERAS cohort. This represents the third independent study correlating genotype at the <i>TRAF1/C5</i> locus with radiological severity in RA. Replication in a large dataset is required to establish the role of other RA susceptibility loci in disease severity. <h3>Disclosure of Interest</h3> None Declared
Abstract C77: A mesenchymal-like subpopulation within squamous cell carcinomas with chemotherapy resistance and phenotypic plasticity
Authors: Devraj Basu, Thierry-Thien Nguyen, Kathleen Montone, Gao Zhang, Li Ping Wang, Anil Rustgi, John Lee, Gregory Weinstein, Meenhard Herlyn
Journal: Cancer Research (2009)

Abstract A major barrier to curative therapy for most malignancies is intrinsic drug resistance within discrete tumor cell subpopulations, which are presently ill-defined. Previous studies show that carcinoma cell lines abundantly expressing mesenchymal markers have increased resistance to both conventional chemotherapy and epidermal growth factor receptor (EGFR)-targeted agents. However it is unclear whether small mesenchymal-like subpopulations contribute to therapy resistance in individual carcinomas with predominantly epithelial features. Here we identified a mesenchymallike subset expressing low E-cadherin (Ecad lo) and high vimentin (Vim hi) within human squamous cell carcinomas of the esophagus (ESCC) and head and neck (HNSCC). This minority subset was readily isolated from two HNSCC lines (SCC9 and OCTT2) and was identifiable in vivo, not only in mouse xenografts of these lines but also in the clinical specimen from which a HNSCC cell line (OCTT2) was derived. The minority Ecad lo/Vim hi subset contained more low-turnover cells and was less proliferative overall, correlating with increased resistance to the conventional chemotherapeutic agent paclitaxel. The Ecad lo/Vim hi subpopulation also demonstrated diminished activity in the MAP kinase/PI3-kinase pathways, likely arising from decreased EGFR expression and correlating with increased in vitro resistance to the EGFR-targeted agent, cetuximab. This mesenchymal-like subpopulation displayed comparable drug resistancein vivo, becoming enriched by cetuximab treatment in a mouse xenograft derived directly from a clinical HNSCC specimen. Furthermore, the Ecad lo/Vim hi and Ecad hi/Vim lo subsets were dynamic and reversible in their phenotypes, showing the capacity to repopulate each other from single cell clones. Taken together, these results show that a low-turnover, mesenchymal-like subpopulation in squamous cell carcinomas has diminished EGFR pathway function and elevated intrinsic resistance to both conventional and targeted chemotherapies. They further suggest that this mesenchymal-like subset retains the plasticity to repopulate other malignant subpopulations post therapy. Citation Information: Cancer Res 2009;69(23 Suppl):C77.
Abstract 4550: NT5E promoter methylation is a favorable breast cancer epigenetic biomarker
Authors: Cristiana Lo Nigro, Martino Monteverde, Sonia Lee, Laura Lattanzio, Nelofer Syed, Ornella Garrone, Marco Merlano, Eleftheria Hatzimichael, Evangelos Briasoulis, Alastair Thompson, Tim Crook
Journal: Cancer Research (2012)

Abstract Despite the recent introduction of advanced microarray-based gene expression profiling strategies, relapse risk assessment and individual treatment recommendations remain suboptimal for breast cancer patients. DNA methylation emerges as a novel source of epigenetic biomarkers that can help improve individualised breast cancer therapy. In the light of existing preclinical and clinical data we studied NT5E (5′-nucleotidase, ecto) expression and NT5E promoter methylation (NPM) in 14 breast cancer cell lines and 259 breast cancer clinical cases. In vitro, NT5E promoter methylation (as determined by MSP and pyrosequencing) was inversely associated with NT5E expression (as determined by qRT-PCR) and azacytidine produced an increase in NT5E mRNA levels in cell lines with methylated the NT5E promoter CpG. In clinical series, patients whose resected primary tumours were found to have NT5E promoter methylation, were less likely to develop metastasis (p=0.003, OR=0.34, 95% CI 0.17-0.69). Moreover in 3 out of 4 paired samples, NT5E promoter was found methylated in primary tumours and demethylated in CNS metastases. Regarding metastatic profile, patients that progressed to non-visceral metastases were more likely to have NT5E promoter methylated in primary tumours as compared to visceral metastatic disease (p=0.01, OR=11.8). NT5E promoter CpG island was densely methylated in 16 of 21 patients who developed non-visceral metastatic disease (76%) and in 6/28 cases (21%) with visceral metastases. In time-dependent endpoints analysis, patients with tumours lacking detectable NT5E methylation had increased risk for shorter DFS (p=0.001, HR 2.7) and OS (p=0.001, HR=3). The favourable prognostic value of NT5E methylation was confirmed in ER negative (p=0.011, HR=3.27, 95% CI 1.31-8.12) and in triple negative cases (p=0.004; HR=6.2, 95% CI 1.9-20). Moreover we observed a strikingly favourable outcome to adjuvant chemotherapy in patients with tumours profiled as NT5E promoter methylated regarding DFS (p=0.0016, HR 5.1, 95% CI 1.8-14.37) and OS (p=0.0005, HR 7.4, 95% CI 2.416 –23.08), which allows speculations that NPM may convey breast cancers more amenable to chemotherapy, possibly though pro-apoptotic mechanism. We suggest that NT5E promoter CpG island methylation may serve as a promising favourable breast cancer epigenetic biomarker. Our results warrant independent confirmation by other groups before considering its investigation as a metastasis predictor in clinical trials of adjuvant breast cancer therapies. 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 4550. doi:1538-7445.AM2012-4550
P440Targeting subcellular GRK2 localization
Authors: A Anastasio, AL Carillo, M Ciccareli, B Trimarco, G Iaccarino, D Sorriento
Journal: Cardiovascular Research (2014)

GRK2 is a kinase involved in the regulation of G protein coupled receptor signaling and in particular phosphorylates beta adrenergic receptors at plasma membrane leading to desensitization. In animal and human models of heart failure, its increased level and activity are associated with a worse prognosis. Recent findings show that GRK2 localizes into mitochondria where it plays a protective role on cell function by promoting biogenesis and increasing ATP production. Aim of this study is to identify the minimum effective sequence of the pleckstrin homology domain of GRK2 (PH), able to displace the kinase from plasma membrane and favour its localization into mitochondria.
Abstract 4434: Thermally targeted delivery of a c-Myc inhibitory peptide to breast tumors in vivo using elastin-like polypeptide
Authors: Gene L. Bidwell, Eddie Perkins, Drazen Raucher
Journal: Cancer Research (2011)

Abstract Although surgical resection with adjuvant chemotherapy and/or radiotherapy are used to treat breast tumors, normal tissue tolerance, development of metastases, and inherent tumor resistance to radiation or chemotherapy can hinder a successful outcome. Therefore, it is necessary to consider alternative targeted therapeutic approaches for adjuvant therapy that would significantly reduce undesired side effects in normal tissues. We have developed a thermally responsive polypeptide (CPP-ELP-H1) that inhibits breast cancer cell proliferation by blocking the activity of the oncogenic protein c-Myc. When administered IV into mice bearing orthotopic, syngeneic breast tumors, CPP-ELP-H1 exhibited a long plasma half life and accumulated in tumor tissue. The tumor levels of the CPP-ELP delivered H1 peptide were enhanced when hyperthermia was applied to the tumor site. Daily administration (7 days) of CPP-ELP-H1 followed by tumor heating induced over 70% reduction in tumor volume compared to unheated controls or controls lacking the H1 inhibitory peptide. This work provides a new modality for targeted delivery of a specific oncogene inhibitor. In addition to the peptide's intrinsic tumor targeting due to its oncogene inhibition, ELP can be physically targeted to the tumor site by application of external hyperthermia. Specific targeting of the proposed therapeutic polypeptides by local hyperthermia to breast tumors or to areas of potential metastasis following tumor resection would increase specificity and efficacy of treatment and reduce the cytotoxicity in normal tissues. 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 4434. doi:10.1158/1538-7445.AM2011-4434
Massive pneumoperitoneum after argon plasma coagulation
Authors: G. de Roberto, D. Ravizza, G. Fiori, C. Trovato, A. de Leone, D. Tamayo, C. Crosta
Journal: Endoscopy (2010)

Argon plasma coagulation (APC) is a noncontact electrocoagulation technique widely used in the gastrointestinal tract. The rate of complications after APC is low even though colonic perforation has been reported after development of submucosal emphysema [1] [2].