tbuckley/cabot-search huggingface dataset:
Abstract 2651: Cucurbitacin I (JSI-124) activates the JNK signaling pathway leading to transcriptional up-regulation of vascular endothelial growth factor in B leukemia cells
Authors: Ganchimeg Ishdorj, James B. Johnston, Spence B. Gibson
Journal: Cancer Research (2011)

Abstract JSI-124 (Cucurbitain I) is a biochemical compound isolated from the herbal plant families, which have been used as folk medicines for centuries in Asian countries. The molecular mechanisms for this inhibitor acts primarily through STAT3 inhibition in many tumors, including chronic lymphocytic leukemia. However, other molecular targets of JSI-124 are not fully understood. The objective of this study was to determine the molecular targets of JSI-124 beyond STAT3. Chemotherapeutic drugs often induce a stress response in cancer cells. One of early stress response pathways is the c-Jun N-terminal kinase (JNK) pathway. Herein, we show that JSI-124 activates JNK and increased the expression of c-Jun protein in the B leukemia cell lines BJAB, I-83 and NALM-6. Interestingly, the inhibition of the JNK signaling pathway failed to effect JSI-124 induced cell cycle arrest or apoptosis in these leukemia cells but repressed c-Jun level. Furthermore, JNK activation also failed to effect JSI-124 inhibition of STAT3 phosphorylation in these cells. It is known that one of the important factors involved in JNK signaling is Vascular Endothelial Growth Factor (VEGF). We found that JSI-124 treated BJAB cells showed an increased in mRNA and protein level in VEGF in BJAB, I-83 and NALM-6 cells. Knockdown of c-Jun expression and inhibition of JNK activation significantly blocked JSI-124 induced VEGF expression. Taken together, our data demonstrate that JSI-124 activates JNK signaling pathway leading to VEGF expression independent of inhibition of STAT3 activation. This could lead to increased angiogenesis in B leukemia cells treated with JSI-124. 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 2651. doi:10.1158/1538-7445.AM2011-2651
Exogenous Reinfection with Tuberculosis in a Shelter for the Homeless
Authors: E. Nardell, B. McInnis, B. Thomas, S. Weidhaas
Journal: New England Journal of Medicine (1986)

We investigated an outbreak of tuberculosis in a large shelter for the homeless to assess the role of exogenous reinfection as opposed to reactivation of endogenous infection as the cause of secondary tuberculosis in this population. Exogenous reinfection is considered relatively unimportant in the United States and other developed countries. Of 49 shelter-related cases, 22 had cultures resistant to both isoniazid and streptomycin and of the same phage type, indicating recent transmission originating with a single index patient. The probable index patient had a 10-year history of isoniazid and streptomycin resistance--an uncommon pattern at the shelter during the three years preceding the outbreak. In 4 of the 22 cases, the patient had previously had documented tuberculosis infection or disease. These reinfected patients had extensive lung cavitation and numerous acid-fast bacilli on sputum smears--features associated with contagiousness. In contrast, patients with tuberculosis for the first time (primary tuberculosis) are usually less contagious. We conclude that exogenous reinfection may have been an important factor leading to highly contagious secondary cases and an acceleration of the usual pattern of tuberculosis transmission in this highly susceptible population.
P1122 COMPARISONS OF POPULATIONS IN FALDAPREVIR PHASE III STUDIES BASED ON PEGYLATED INTERFERON a-2a AND RIBAVIRIN-PREDICTED RESPONSIVENESS AND IMPACT ON ACHIEVING SVR12
Authors: P. Ferenci, D.M. Jensen, D. Dieterich, I.M. Jacobson, M. Romero-Gómez, G.R. Foster, T. Asselah, C. Cooper, C. Tural, A. Streinu-Cercel, S. Ryder, M. Puoti, E. Tam, J.L. Calleja, M. Núñez, A.-M. Quinson, W. Böcher, F. Voss, J. Scherer
Journal: Journal of Hepatology (2014)
Quantitative texture analysis of EUS images accurately differentiates pancreatic cancer from normal tissue and may obviate the need for EUS-FNA
Authors: A Das, F Li, C Nguyen
Journal: Endoscopy (2006)

Texture analysis as an approach to tissue characterization based on the two-dimensional spatial distribution of ultrasound amplitude or grey-level pixels within a region of interest (ROI) is well-established and have been used extensively in Radiology and echocardiography. Objective: We performed a quantitative statistical analysis of various texture parameters of EUS images in patients with histologically confirmed pancreatic adenocarcinoma to evaluate if such statistical techniques can reliably distinguish between malignant and normal pancreatic tissue. Methods: Linear endosonographic images of 22 patients who presented with pancreatic mass and underwent EUS guided FNA for establishing diagnosis of pancreatic adenocarcinoma were analyzed with an image analyzing software (ImageJ, NIH). Multiple ROIs were digitally selected both in the area of the malignant mass and normal pancreatic tissue by an experienced endosonographer. Texture analysis was performed using: histogram (first order statistics) run-length and co-occurrence matrix (measuring features of runs of pixels and distribution of pairs of pixels), gradient analysis (spatial distribution of pixels), auto-regressive analysis (measurement of local interaction amongst pixels of different grey level values) and also wavelet analysis (which measures parameters of spatial frequency). A neural network (NN) based predictive model was built, trained and validated using the extracted texture features for classification of malignant tissue from normal. Methods: A total of 70 ROIs representing malignant tissue and 110 representing normal pancreatic tissue was available for analysis and for each ROI, a total 256 statistical parameters were initially extracted and subsequently 10 best discriminating (based on highest Fisher's co-efficient) features were retained. Overall, 3 types of features had high discriminatory power: Kurtosis (which is a measure of the steepness of the pixel distribution), angular second momentum and horizontal and vertical grey level non-uniformity (parameters estimating the second order joint conditional probability density functions of spatial distribution of two neighboring pixels). Using a random selection of the half of the data set (90 ROIs), a multi-layered perceptron NN model was built, trained using the 10 features as input variables for prediction of malignant tissue and then the model was validated on the rest of the 90 ROIs. The NN model had a very high classification performance with an area under Receiver Operating Characteristic Curve of 0.91 (PPV of 80% and NPV 90%). Conclusion: Digital image analysis of texture features on EUS images is highly accurate in differentiating malignant from normal pancreatic tissue with performance characteristics similar to aspiration cytology.
Distinctive Patterns of Super Scan Appearance in Bone Metastasis and Hyperthyroidism
Authors: M Koizumi, S Matsumoto
Journal: Clinical Nuclear Medicine (1998)

Two cases of a so-called super scan are presented. The first patient showed a super scan in hyperthyroidism. The second patient showed a super scan in diffuse bone metastases. There is a distinct difference between the accumulation patterns in the two patients. In the patient with hyperthyroidism, increased uptake was distributed evenly in the long bones. However, in the patient with diffuse bone metastases, increased uptake was seen in the proximal portions of the long bones (femur and humerus). The latter pattern is derived from the distribution of the red bone marrow, and the uptake in the proximal humerus and femur is an important consideration when differentiating diffuse bone metastases from metabolic bone disease.
Abstract 1069: Mutant p53 disrupts the role of ShcA in balancing the Smad-dependent and -independent signaling activity of TGF-β
Authors: Shu Lin, Lan Yu, Junhua Yang, Zhao Liu, Bijal Karia, Alexander J. R. Bishop, James Jackson, Guillermina Lozano, John A. Copland, Xiaoxin Mu, Beicheng Sun, Lu-Zhe Sun
Journal: Cancer Research (2012)

Abstract Biomarkers are lacking for identifying the switch of transforming growth factor-beta (TGF-β) from tumor-suppressing to tumor-promoting. Mutated p53 (mp53) has been suggested to switch TGF-β to a tumor promoter. However, we found that mp53 does not always promote the oncogenic role of TGF-β. Here, we show that endogenous mp53 knockdown enhanced cell migration and phosphorylation of ERK in DU145 prostate cancer cells. Further, ectopic expression of mp53 in p53-null PC-3 prostate cancer cells enhanced Smad-dependent signaling, but inhibited TGF-β-induced cell migration by downregulating activated ERK. Reactivation of ERK by the expression of its activator, MEK-1, restored TGF-β-induced cell migration. Since TGF-β is known to activate MAPK/ERK pathway through direct phosphorylation of adaptor protein ShcA and MAPK/ERK signaling is pivotal to tumor progression, we investigated whether ShcA contributed to mp53-induced ERK inhibition and the conversion of TGF-β's role during carcinogenesis. We found that mp53 expression led to decrease of phosphorylated p52ShcA/ERK levels and increase of phosphorylated Smad levels in a panel of mp53-expressing cancer cell lines, and in mammary glands and tumors from mp53 knock-in mice. By manipulating ShcA levels to regulate ERK and Smad signaling in human untransformed and cancer cell lines, we show that TGF-β's role in regulating anchorage-dependent and -independent growth, and migration, can be shifted between growth suppression and migration promotion. Thus, our results, for the first time, suggest that mp53 disrupts ShcA's role in balancing Smad-dependent and -independent signaling activity of TGF-β and that ShcA/ERK signaling is a major pathway regulating the tumor-promoting activity of TGF-β. 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 1069. doi:1538-7445.AM2012-1069
SAT0228 Performance of MRI Compared to Conventional Radiographs in the Detection of Structural Lesions in the Sacroiliac Joints in Patients With Recent Onset Axial Spondyloarthritis
Authors: R. van den Berg, M. de Hooge, V. Navarro Compán, M. Reijnierse, F. van Gaalen, K. Fagerli, R. Landewé, M. van Oosterhout, M. Lorenzin, T. Huizinga, D. van der Heijde
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Structural lesions are visible on MRI T1-weighted images of the sacroiliac (SI) joints. However, radiographs are currently the established method to detect structural lesions (SL). <h3>Objectives</h3> To compare the performance of MRI to radiographs in detecting SL in the SI-joints. <h3>Methods</h3> The SPondyloArthritis Caught Early (SPACE)-cohort includes patients (pts) with back pain (≥3 months, ≤2 years, onset &lt;45 years) from the 5 participating centers. Pts underwent MRI and radiographs of the SI-joints (MRI-SI and X-SI, resp). MRI-SI (T1-weighted images; STIR viewed simultaneously) and X-SI were scored by 3 well-calibrated readers independently on the presence of erosions, sclerosis and ankylosis. Erosions and sclerosis were defined according to the MORPHO definition<sup>1</sup> (≥1 lesion on ≥2 consecutive slices or ≥2 lesion on 1 slice). Ankylosis was defined as ≥1 lesion on ≥1 slice. Lesions were considered present if 2/3 readers agreed. MRI was considered positive for SL (MRI-SI-s+) if ≥4 or ≥5 SL (any type) were present. Comparisons between MRI-SI and X-SI using crosstabs (Kappa) were done for erosions, sclerosis, ankylosis and for MRI-SI-s+ versus modified New York (mNY) score<sup>2</sup>. <h3>Results</h3> Pts with complete MRI-SI and X-SI data (n=279) were included (558 SI-joints). Kappas and % agreement for all SL are presented on patient and SI-joint level (table). Despite high levels of agreement (e.g. 96.4% for ankylosis), the kappas for the comparison of all SL on MRI-SI and X-SI were rather low. This discrepancy is well known if abnormalities are infrequent: if there are no abnormalities agreement is high, yet positive findings are infrequently seen on both imaging modalities. Erosions were more frequently detected on MRI only; sclerosis and ankylosis more frequently on X-SI. MRI-SI-s+ was more frequent than mNY. <h3>Conclusions</h3> In pts with recent onset axSpA, including a high number of pts without lesions, the agreement in detecting SL on MRI-SI and X-SI is poor. Overall, more SL are detected on MRI. More research on what findings on both modalities truly mean is required in order to determine their respective places in diagnosing and classifying pts. <h3>References</h3> Weber A&amp;R 2010;62:3048-58 van der Linden A&amp;R 1984;27:361–8 <h3>Disclosure of Interest</h3> None Declared
Location on Chromosome 15 of the Gene Defect Causing Marfan Syndrome
Authors: Katariina Kainulainen, Leena Pulkkinen, Aslak Savolainen, Ilkka Kaitila, Leena Peltonen
Journal: New England Journal of Medicine (1990)

Marfan syndrome, "the founding member" of the heritable disorders of connective tissue, is a common autosomal dominant disorder with highly variable clinical manifestations in the skeletal, ocular, and cardiovascular systems. The fundamental defect leading to this disease has escaped definition despite decades of research efforts by several groups of investigators.
THU0494 Meta-Analysis of Differentially Expressed Genes in Ankylosing Spondylitis
Authors: Y.H. Lee, S.J. Choi, J.D. Ji, G.G. Song
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Microarrays measure the expression of thousands of genes simultaneously on a genome-wide scale. Alterations in genetic profiles can be correlated to altered gene functions and biochemical activities. Although many microarray studies have produced lists of differentially expressed (DE) genes, there tend to be inconsistencies between studies due to the limitations of small sample sizes and variable results. <h3>Objectives</h3> The purpose of this study was to identify differentially expressed (DE) genes and biological processes associated with changes in gene expression in ankylosing spondylitis (AS) using meta-analysis approach. <h3>Methods</h3> We performed a meta-analysis using the integrative meta-analysis of expression data (INMEX) program on publicly available microarray AS Gene Expression Omnibus (GEO) datasets. We performed Gene Ontology (GO) enrichment analyses and pathway analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG). <h3>Results</h3> Four GEO datasets, including 31 cases and 39 controls, were available for the meta-analysis. We identified 65 genes across the studies that were consistently DE in AS cases vs. controls (23 up-regulated and 42 down-regulated). The up-regulated gene with the largest effect size (ES; -1.2628, P=0.020951) was <i>ITM2A</i> (integral membrane protein 2A), which is expressed by CD4+ T cells and plays a role in activation of T cells. The up-regulated gene with the lowest P-value (0.005673) was <i>TGFBR3</i> (transforming growth factor beta receptor III), which is a true BMD-associated gene as part of the TGF pathway. The down-regulated gene with the largest ES (1.2299, P=0.040075) was <i>MRPS11</i> (mitochondrial ribosomal protein S11). The most significant GO enrichment was in the respiratory electron transport chain category (P=1.67x10<sup>–9</sup>). <h3>Conclusions</h3> Our meta-analysis identified genes including <i>ITM2A</i> and <i>TGFBR3</i> that were consistently DE and biological pathways associated with gene expression changes in AS. <h3>References</h3> Xia J, Fjell CD, Mayer ML, Pena OM, Wishart DS, Hancock RE. INMEX–a web-based tool for integrative meta-analysis of expression data. Nucleic Acids Res. 2013;41(W1):W63-W70. <h3>Disclosure of Interest</h3> : None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1187
Intrinsic Radiation Sensitivity: No Correlation With the Metastatic Potential of Human and Murine Tumor Cell Lines
Authors: A. Allam, D. Gioioso, A. Taghian, M. Duffy, I. J. Fidler, H. D. Suit
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Intrinsic Radiation Sensitivity: No Correlation With the Metastatic Potential of Human and Murine Tumor Cell Lines Get access Ayman Allam, Ayman Allam Edwin L. Steele, Laboratory of Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical SchoolBoston, Mass Correspondence to : Ayman Allam, M.D., Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114. Search for other works by this author on: Oxford Academic PubMed Google Scholar Danielle Gioioso, Danielle Gioioso Edwin L. Steele, Laboratory of Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical SchoolBoston, Mass Search for other works by this author on: Oxford Academic PubMed Google Scholar Alphonse Taghian, Alphonse Taghian Edwin L. Steele, Laboratory of Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical SchoolBoston, Mass Search for other works by this author on: Oxford Academic PubMed Google Scholar Michael Duffy, Michael Duffy Edwin L. Steele, Laboratory of Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical SchoolBoston, Mass Search for other works by this author on: Oxford Academic PubMed Google Scholar Isaiah J. Fidler, Isaiah J. Fidler Department of Cell Biology, The University of Texas M. D. Anderson Cancer CenterHouston, Tex Search for other works by this author on: Oxford Academic PubMed Google Scholar Herman D. Suit Herman D. Suit Edwin L. Steele, Laboratory of Radiation Biology, Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical SchoolBoston, Mass * See “Notes” section following “References.” Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 23, 1 December 1993, Pages 1954–1957, https://doi.org/10.1093/jnci/85.23.1954 Published: 01 December 1993 Article history Received: 03 June 1993 Revision received: 20 July 1993 Accepted: 26 August 1993 Published: 01 December 1993
A1.21 In-depth characterisation of CD24highCD38high transitional human B cells reveals different regulatory profiles
Authors: S Hillion, Q Simon, D Cornec, R Mageed, JO Pers
Journal: Annals of the Rheumatic Diseases (2015)

<h3></h3> CD24high CD38high transitional B cells represent a key stage in the developmental pathway of B cell peripheral tolerance and functional maturation. These B cells have been widely ascribed regulatory functions. However, the phenotypic and functional overlap between these cells and regulatory B cells remains controversial. In this study, we use multi-colour flow cytometry with bioinformatic analyses and functional studies to show that CD24high CD38high B cells can be differentiated into multiple subsets. The study also reveals for the first time that human transitional B cells encompass transitional type 1 (T1) and T2 B cells but also distinct anergic T3 B cells as well as IL-10-producing CD27<sup>+</sup> transitional B cells. Interestingly, the latter two subsets differentially regulate CD4<sup>+</sup> T cell proliferation and polarisation towards Th1 effector cells. Additional analyses show that the percentage of T3 B cells is reduced while the frequency of CD27<sup>+</sup> transitional B cells is increased in patients with autoimmune diseases compared with matched healthy individuals. This study provides evidence for the existence of different transitional B cell subsets each displaying unique phenotypic and regulatory functional profiles. Furthermore, the study indicates that altered distribution of transitional B cells subsets highlights different regulatory defects in autoimmune diseases
Natural Killer Cell Activity: Age, Estrous-and Circadian-Stage Dependence and Inverse Correlation With Metastatic Potential
Authors: W. J. M. Hrushesky, S. A. Gruber, R. B. Sothern, R. A. Hoffman, D. Lakatua, A. Carlson, F. Cerra, R. L. Simmons
Journal: JNCI Journal of the National Cancer Institute (1988)

Journal Article Natural Killer Cell Activity: Age, Estrous-and Circadian-Stage Dependence and Inverse Correlation With Metastatic Potential Get access William J. M. Hrushesky, William J. M. Hrushesky * 3Department of Medicine, University of Minnesota HospitalsMinneapolis, MN.4Departments of Laboratory Medicine and Pathology. (W. J. M. Hrushesky, D. Lakatua), Biomedical Engineering (W. J. M. Hrushesky), and Surgery (S. A. Gruber, A. Carlsom, F. Cerra), University of MinnesotaMinneapolis, MN. *Correspondence to: Dr. William J. M. Hrushesky, Department of Medicine, Box 414, University of Minnesota Hospital and Clinic, University of Minnesota, Minneapolis, MN 55455. Search for other works by this author on: Oxford Academic PubMed Google Scholar Scott A. Gruber, Scott A. Gruber 4Departments of Laboratory Medicine and Pathology. (W. J. M. Hrushesky, D. Lakatua), Biomedical Engineering (W. J. M. Hrushesky), and Surgery (S. A. Gruber, A. Carlsom, F. Cerra), University of MinnesotaMinneapolis, MN. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert B. Sothern, Robert B. Sothern 3Department of Medicine, University of Minnesota HospitalsMinneapolis, MN. Search for other works by this author on: Oxford Academic PubMed Google Scholar Rosemary A. Hoffman, Rosemary A. Hoffman 5Department of Surgery, University of PittsburghPittsburgh, PA 15261 Search for other works by this author on: Oxford Academic PubMed Google Scholar David Lakatua, David Lakatua 4Departments of Laboratory Medicine and Pathology. (W. J. M. Hrushesky, D. Lakatua), Biomedical Engineering (W. J. M. Hrushesky), and Surgery (S. A. Gruber, A. Carlsom, F. Cerra), University of MinnesotaMinneapolis, MN. Search for other works by this author on: Oxford Academic PubMed Google Scholar Ann Carlson, Ann Carlson 4Departments of Laboratory Medicine and Pathology. (W. J. M. Hrushesky, D. Lakatua), Biomedical Engineering (W. J. M. Hrushesky), and Surgery (S. A. Gruber, A. Carlsom, F. Cerra), University of MinnesotaMinneapolis, MN. Search for other works by this author on: Oxford Academic PubMed Google Scholar Frank Cerra, Frank Cerra 4Departments of Laboratory Medicine and Pathology. (W. J. M. Hrushesky, D. Lakatua), Biomedical Engineering (W. J. M. Hrushesky), and Surgery (S. A. Gruber, A. Carlsom, F. Cerra), University of MinnesotaMinneapolis, MN. Search for other works by this author on: Oxford Academic PubMed Google Scholar Richard L. Simmons Richard L. Simmons 5Department of Surgery, University of PittsburghPittsburgh, PA 15261 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 80, Issue 15, 5 October 1988, Pages 1232–1237, https://doi.org/10.1093/jnci/80.15.1232 Published: 05 October 1988 Article history Received: 12 July 1988 Accepted: 13 July 1988 Published: 05 October 1988