tbuckley/cabot-search huggingface dataset:
WNT16 antagonises excessive canonical WNT activation and protects cartilage in osteoarthritis
Authors: Giovanna Nalesso, Bethan Lynne Thomas, Joanna Claire Sherwood, Jing Yu, Olga Addimanda, Suzanne Elizabeth Eldridge, Anne-Sophie Thorup, Leslie Dale, Georg Schett, Jochen Zwerina, Noha Eltawil, Costantino Pitzalis, Francesco Dell'Accio
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objective</h3> Both excessive and insufficient activation of WNT signalling results in cartilage breakdown and osteoarthritis. WNT16 is upregulated in the articular cartilage following injury and in osteoarthritis. Here, we investigate the function of WNT16 in osteoarthritis and the downstream molecular mechanisms. <h3>Methods</h3> Osteoarthritis was induced by destabilisation of the medial meniscus in wild-type and WNT16-deficient mice. Molecular mechanisms and downstream effects were studied in vitro and in vivo in primary cartilage progenitor cells and primary chondrocytes. The pathway downstream of WNT16 was studied in primary chondrocytes and using the axis duplication assay in Xenopus. <h3>Results</h3> WNT16-deficient mice developed more severe osteoarthritis with reduced expression of lubricin and increased chondrocyte apoptosis. WNT16 supported the phenotype of cartilage superficial-zone progenitor cells and lubricin expression. Increased osteoarthritis in WNT16-deficient mice was associated with excessive activation of canonical WNT signalling. In vitro, high doses of WNT16 weakly activated canonical WNT signalling, but, in co-stimulation experiments, WNT16 reduced the capacity of WNT3a to activate the canonical WNT pathway. In vivo, WNT16 rescued the WNT8-induced primary axis duplication in Xenopus embryos. <h3>Conclusions</h3> In osteoarthritis, WNT16 maintains a balanced canonical WNT signalling and prevents detrimental excessive activation, thereby supporting the homeostasis of progenitor cells.
Pet-Imaging with 89Zr-Labeled Anti-Mesothelin (Msln) Antibody in Patients with Pancreatic Cancer (Pc) or Ovarian Cancer (Oc)
Authors: L.E. Lamberts, C.W. Menke-van der Houven van Oordt, F. Bensch, J. Voortman, O.S. Hoekstra, D. Maslyar, S.P. Williams, B.M. Fine, A.H. Bongaerts, J.A. Gietema, C.P. Schroder, E.J. r Te Weele, M.N. Lub-De Hooge, H.M. Verheul, S. Sanabria, A.W.J.M. Glaudemans, E. De Vries
Journal: Annals of Oncology (2014)
PU.1 controls the expression of long noncoding RNA HOTAIRM1 during granulocytic differentiation
Authors: Shuyong Wei, Ming Zhao, Xiaoling Wang, Yizhen Li, Kankan Wang
Journal: Journal of Hematology & Oncology (2016)

Long noncoding RNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) has been characterized as a critical factor in all-trans retinoic acid (ATRA)-induced differentiation of acute promyelocytic leukemia (APL) cells. However, the essential transcription factor for gene expression of HOTAIRM1 is still unknown. Chromatin immunoprecipitation (ChIP) assays revealed that PU.1 constitutively bound to the regulatory region of HOTAIRM1. Co-expression of PU.1 led to the transactivation of the regulatory region of HOTAIRM1 in a reporter assay. Detailed analysis showed that two PU.1 motifs, which were located around +1100 bp downstream of the transcriptional start site of the HOTAIRM1 promoter, were responsible for the PU.1-dependent transactivation. The induction of HOTAIRM1 by ATRA was dependent on PU.1, and ectopic expression of PU.1 significantly up-regulated HOTAIRM1. Furthermore, low HOTAIRM1 expression was observed in APL cells, which was attributed to the reduced PU.1 expression rather than the repression by PML-RARα via the direct binding. PU.1 directly activates the expression of HOTAIRM1 through binding to the regulatory region of HOTAIRM1 during granulocytic differentiation. The reduced PU.1 expression, rather than PML-RARα itself, results in the low expression of HOTAIRM1 in APL cells. Our findings enrich the knowledge on the regulation of lncRNAs and the underlying mechanisms of the abnormal expression of lncRNAs involved in APL.
Somatic and Germ-Line Molecular Characteristics Of Prefibrotic Myelofibrosis
Authors: Giovanni Barosi, Elisa Bonetti, Paolo Catarsi, Margherita Massa, Rita Campanelli, Valentina Poletto, Gianluca Viarengo, Laura Villani, Gabriela Fois, Flavia Biamonte, Giada Rotunno, Paola Guglielmelli, Umberto Magrini, Alessandro M Vannucchi, Vittorio Rosti
Journal: Blood (2013)
Elevated Bladder Cancer in Northern New England: The Role of Drinking Water and Arsenic
Authors: Dalsu Baris, Richard Waddell, Laura E Beane Freeman, Molly Schwenn, Joanne S Colt, Joseph D Ayotte, Mary H Ward, John Nuckols, Alan Schned, Brian Jackson, Castine Clerkin, Nathaniel Rothman, Lee E Moore, Anne Taylor, Gilpin Robinson, Gm Monawar Hosain, Karla R Armenti, Richard McCoy, Claudine Samanic, Robert N Hoover, Joseph F Fraumeni, Alison Johnson, Margaret R Karagas, Debra T Silverman
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: Bladder cancer mortality rates have been elevated in northern New England for at least five decades. Incidence rates in Maine, New Hampshire, and Vermont are about 20% higher than the United States overall. We explored reasons for this excess, focusing on arsenic in drinking water from private wells, which are particularly prevalent in the region.
Abstract 5049: Checkpoint kinase 2 is a novel regulator of prostate cancer cell growth
Authors: Huy Q. Ta, Melissa L. Ivey, Henry F. Frierson, Mark R. Conaway, Jaroslaw Dziegielewski, James M. Larner, Daniel Gioeli
Journal: Cancer Research (2015)

Abstract Prostate cancer (PCa) is the second leading cause of cancer death in American men, and the cure for metastatic disease remains a significant challenge. While nearly all patients with disseminated PCa initially respond to androgen deprivation therapy (ADT), virtually every patient will relapse and develop incurable castration-resistant prostate cancer (CRPC). Androgen receptor (AR) signaling pathways continue to play a crucial role in CRPC progression. Previous studies have shown that signal transduction pathways can stimulate AR activation, suggesting that the ability of signaling cascades to influence AR function may have a significant role in CRPC progression, and that CRPC may not be effectively treated by ligand-directed therapy alone. A high-throughput RNAi screen identifying signaling pathways that regulate PCa cell growth led to our discovery that knockdown of Checkpoint Kinase 2 (CHK2) dramatically increased PCa proliferation in the presence and absence of androgen. Furthermore, CHK2 depletion hypersensitized cells to castrate androgen levels. These CHK2-mediated effects on growth were dependent on the downstream signaling proteins CDC25C and CDK1 and could be blocked by the AR antagonist MDV3100. Immunohistochemical analysis of CHK2 in patient samples demonstrated that reduced CHK2 expression significantly correlated with increased Gleason score indicating the clinical relevance of CHK2 in PCa. Moreover, CHK2 expression is lower in castration-resistant C4-2 and CWR22Rv1 cells compared to androgen-sensitive LNCaP cells consistent with loss of CHK2 expression during PCa progression. CHK2 depletion increased AR transcriptional activity on both androgen-activated and androgen-repressed genes, substantiating that CHK2 affects PCa growth through the AR. Remarkably, quantitative PCR, chromatin immunoprecipitation, and western blot analyses revealed that CHK2 is a novel AR-repressed gene, suggesting a negative feedback loop between CHK2 and the AR. Furthermore, we show that CHK2 physically associates with the AR, and that cellular stress, such as DNA damage and serum starvation, increases this association. Based on these data, we propose that CHK2 is a negative regulator of androgen sensitivity and PCa growth. Thus, alterations to CHK2 signaling may sensitize CRPC to ADT and radiation. Citation Format: Huy Q. Ta, Melissa L. Ivey, Henry F. Frierson, Mark R. Conaway, Jaroslaw Dziegielewski, James M. Larner, Daniel Gioeli. Checkpoint kinase 2 is a novel regulator of prostate cancer cell growth. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5049. doi:10.1158/1538-7445.AM2015-5049
Acetylcholine polarizes dendritic cells toward a Th2-promoting profile
Authors: S. Gori, M. Vermeulen, F. Remes-Lenicov, C. Jancic, W. Scordo, A. Ceballos, N. Towstyka, Y. Bestach, C. Belli, F. Sabbione, J. Geffner, G. Salamone
Journal: Allergy (2016)

Background A growing body of research shows a reciprocal regulation between the neural and immune systems. Acetylcholine (ACh) is the most important parasympathetic neurotransmitter, and increasing evidence indicates that it is able to modulate the immune response. Interestingly, in recent years, it has become clear that immune cells express a non-neuronal cholinergic system, which is stimulated in the course of inflammatory processes. We have previously shown that dendritic cells (DC) express muscarinic receptors, as well as the enzymes responsible for the synthesis and degradation of ACh. Here, we analyzed whether ACh could also modulate the functional profile of DC. Methods Dendritic cells were obtained from monocytes cultured for 5 days with GM-CSF+IL-4 or isolated from peripheral blood (CD1c+ DC). The phenotype of DC was evaluated by flow cytometry, the production of cytokines was analyzed by ELISA or intracellular staining and flow cytometry, and the expression of muscarinic and nicotinic receptors was evaluated by flow cytometry or qRT-PCR. Results Treatment of DC with ACh stimulated the expression of the Th2-promoter OX40L, the production of the Th2-chemokines MDC (macrophage-derived chemokine/CCL22) and TARC (thymus and activation-regulated chemokine/CCL17), and the synthesis of IL-4, IL-5, and IL-13 by T cells, in the course of the mixed lymphocyte reaction (MLR). Moreover, we found that the stimulation of OX40L, HLA-DR, and CD83 expressions in DC induced by the Th2-promoting cytokine TSLP, as well as the production of IL-13, IL-4, and IL-5 by T cells in the course of the MLR, was further enhanced when DC were treated with TSLP plus ACh, instead of TSLP or ACh alone. Conclusions Our observations suggest that ACh polarizes DC toward a Th2-promoting profile.
Thinking Beyond Age for Postacute Care After Major Abdominal Surgery
Authors: Anne M. Suskind, Emily Finlayson
Journal: JAMA Surgery (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Farletuzumab, a monoclonal antibody against folate receptor alpha (FRα), does not block folate or anti-folate binding or alter drug potency assessed in vitro.
Authors: B. A. Kamen, A. K. Smith, M. Phillips, L. Grasso
Journal: Journal of Clinical Oncology (2011)

e13544 Background: FRα is overexpressed in a number of carcinomas. It is the target of the humanized monoclonal antibody, farletuzumab (FAR), currently in trials for ovarian and NSCL cancer. Pemetrexed (PMX) is commonly used in NSCLC treatment. Because PMX has a high affinity for FRα, it would be of concern if its accumulation depended on FRα and FAR blocked this process. Prior work using siRNA technology has shown that the cytotoxicity of PMX in FRα + cell lines is not dependent on receptor (Clin Ca Res 2004; 10:7986-93). Methods: Here we assessed the membrane binding, cellular accumulation and the cytotoxicity of PMX as well as methotrexate (MTX) and aminopterin (AMT), anti-folates with a very low affinity for FRα, in cell lines that express FRα [IGROV (ovarian carcinoma), MA104 (kidney epithelial)] or FRα negative Chinese Hamster Ovary (CHO) cells. In addition, since patients are supplemented with folate while taking PMX, we also assessed effects of FAR on the binding and uptake of the predominant plasma folate, 5-methyltetrahydrofolate (CH3FH4). Results: Binding of radiolabeled PMX and CH3FH4 was not blocked by FAR even when pre-incubated for 72 h prior to drug addition. Moreover, when cells were incubated with folic acid (FA), a ligand with such a high affinity for FRα that any cell accumulation of test drug is via a receptor independent mechanism (e.g., reduced folate carrier), there was significant CH3FH4 and PMX uptake, indicating that FRα is not the sole path for transport. FAR did not alter the IC50 of PMX, MTX or AMT, but increasing CH3FH4 from 5 to 40 nM increased the IC50 of PMX from 1.5 to 20 nM. FA (100 nM) increased the IC50 of PMX to 28 nM. Conclusions: Whereas folate decreases the potency of PMX, FAR does not interfere with folate or anti-folate binding by FRα and, moreover, does not alter the potency of anti-folates in vitro. This implies that FAR and small molecules targeting FRα may be used concomitantly if preclinical testing warranted such combinations and that the addition of FAR to a regimen already using PMX would not be expected to result in marked increases in PMX toxicity.
Hereditary pyropoikilocytosis and elliptocytosis in a white French family with the spectrin alpha I/74 variant related to a CGT to CAT codon change (Arg to His) at position 22 of the spectrin alpha I domain
Authors: M Garbarz, MC Lecomte, C Feo, I Devaux, C Picat, C Lefebvre, F Galibert, H Gautero, O Bournier, C Galand
Journal: Blood (1990)
Acute Lymphoblastic Leukemia: Classification and Characterization With Antisera to Human T-Cell and la Antigens&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: J K Anderson, J O Moore, J M Falletta, W F Terry, R S Metzgar
Journal: JNCI Journal of the National Cancer Institute (1979)

Xenoantisera previously shown to detect human Tlymphocyte- associated antigens (TLAA) and la antigens were used to study a group of 26 acute lymphoblastic leukemia (ALL) patients. With the use of a complement-dependent microcytotoxicity assay and sheep erythrocyte (E) rosette formation, ALL cells could be divided into 3 groups. The first group (E+ TLAA+, and la) exhibited a significant number of E-rosette-forming cells (>20%), was strongly reactive with the anti-TLAA sera (>90% lysis at 1:10 dilution), and was negative with the anti-la sera. A second group of cells (E-, TLAA+ and la-) was negative with the anti-Ia sera and formed less than 10% E-rosettes, yet it was strongly reactive with the anti-TLAA sera. The third group of cells (E-, TLAA-, la+) formed less than 5% E-rosettes, was negative with the anti-TLAA sera, and was strongly reactive with the anti-La sera. Representative cells from each group were radiolabeled either with 125I by means of Bolton-Hunter reagent or with 3H by means of galactose oxidase and sodium [3H]borohydride. When sodium deoxycholate-solubilized membrane preparations from these cells were subjected to radioimmunoprecipitation with the use of the anti-TLAA and anti-la sera, the same specificity was seen as was noted by cytotoxicity. Immunoprecipitates were reduced and subjected to sodium dodecyl sulfatepolyacrylamide gel electrophoresis. The antigens with molecular weights of 35,000 and 27,000 daltons precipitated from E-, TLAA-, ta' cells were similar to those precipitated by the anti-Ia sera from known la+ cells. A large (>100,000 daltons) antigen, similar to that precipitated from HSB cells, thymus cells, and peripheral blood lymphocytes, was precipitated from TLAA+ cells by the anti-TLAA sera, regardless of whether or not these cells formed E-rosettes.
<i>Market in San Miguel</i>
Authors: Thomas B. Cole
Journal: JAMA (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
MTR-09ABCB1 AS PREDICTIVE MARKER FOR POOR SURVIVAL IN PATIENTS WITH GLIOBLASTOMA TREATED WITH RADIOTHERAPY AND CONCOMITANT AND ADJUVANT TEMOZOLOMIDE
Authors: Annika Malmström, Martin Hallbeck, Victoria Fomichov, Peter Milos, Anna-Lotta Hallbeck, Charlotte Bratthäll, Michael Strandeus, Angeliki Papagiannopoulou, Svante Vikingsson, Peter Söderkvist, Marie Stenmark-Askmalm, Henrik Green
Journal: Neuro-Oncology (2015)

BACKGROUND: Standard treatment for newly diagnosed glioblastoma (GBM) patients is surgery followed by radiotherapy (RT) and temozolomide (TMZ) given concomitant and adjuvant. Tumor MGMT methylation status has been identified as predictive for response to TMZ. Also other factors are believed to influence TMZ effect. We examined the role of different single nucleotide variants (SNV:s) of ABCB1, a transmembrane drug transporter, for survival for GBM patients receiving RT concomitant with TMZ. PATIENTS AND METHODS: Genomic samples from patients with GBM who received RT + TMZ concomitant was analyzed for SNV:s of ABCB1, namely variants G1199A, C1236T, G2677T_A and C3435T and correlated to overall survival (OS). ABCB1 was determined using DNA from blood. RESULTS: The cohort included 101 patients, diagnosed and treated between 2004 and 2014. Median age was 60 (range 32-74). 83% of patients received RT 60 Gy, 5% 34 Gy and 12% between 40-58 Gy concomitant with TMZ. For SNV G1199A median OS for variant G/G was 18.2 months versus 11.5 months for those with G/A (p = 0.009), while the other SNV:s showed no significant correlation to survival. For 78 patients MGMT status is available. In multivariate analyses MGMT status and G1199A SNV were both independent factors for survival (p = 0.000 and 0.018 respectively). CONCLUSION: For GBM patients receiving RT concomitant with TMZ the ABCB1 SNV G1199A could be a new treatment predictive factor.
Specific Vulnerability of the Largest Telocentric Chromosome of Rat Bone Marrow Cells to 7,12-Dimethylbenz[&lt;italic&gt;a&lt;/italic&gt;]anthracene&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: T Sugiyama
Journal: JNCI Journal of the National Cancer Institute (1971)
Vaccinating pregnant women against flu reduces newborns’ risk of infection, study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

Infants born to women who reported receiving influenza vaccine during pregnancy had a 61% reduction in influenza-like illnesses in the first six months of life, a 70% reduction in laboratory confirmed influenza and an 81% reduction in hospitalisations associated with laboratory confirmed influenza when compared with infants whose mothers did not receive the vaccine during pregnancy, a US study has found.1

Current flu vaccines do not protect infants in the first six months of life because they do not elicit a sufficient immune response in …
Double-balloon enteroscopy-assisted closure of perforated duodenal diverticulum using polyglycolic acid sheets
Authors: Fumisato Sasaki, Shuji Kanmura, Yuichiro Nasu, Shinichi Hashimoto, Hiroki Taguchi, Masatsgu Numata, Akio Ido
Journal: Endoscopy (2015)

Polyglycolic acid (PGA) sheets and fibrin glue adhere firmly and for a long time, are naturally absorbable, and are used in various fields, including endoscopic therapy [1] [2] [3] [4] [5] [6] [7] [8]. We report a case of perforation of a duodenal diverticulum that was treated with an endoscopic tissue-shielding method using PGA sheets and fibrin glue.
Cytotoxic Anticancer Drug Enhances Nk Cell-Mediated Cytotoxicity Via the Dna Stress Induced Nkg2D Ligands in Non-Small-Cell Lung Cancer Cells
Authors: R. Okita, K. Yasuda, A. Maeda, T. Yukawa, S. Saisho, K. Shimizu, M. Nakata
Journal: Annals of Oncology (2014)