tbuckley/cabot-search huggingface dataset:
Nuclear-cytoplasmic interactions affecting DNA synthesis during induced cardiac muscle growth in the rat
Authors: L. B BUGAISKY, M. RABINOWITZ, R. ZAK
Journal: Cardiovascular Research (1985)

Nuclear-cytoplasmic interactions affecting DNA synthesis during induced cardiac muscle growth were examined in 29 to 46 day old rats. DNA synthesis was examined in vitro using isolated nuclei from rat heart and adult X. laevis spleen. Cytoplasmic extract (CE) was obtained from a 105 000 g supernatant of rat heart and fetal liver homogenates. To measure DNA synthesis we utilised DNA within the isolated quiescent nucleus as the template and measured the effect of CE on the incorporation of 3H-TTP into an acid precipitable product. In a homologous system of rat heart nuclei from weanling rats and CE from cardiac muscle undergoing induced growth, no stimulation of 3H-TTP incorporation was observed. Cardiac muscle CE however, did possess stimulatory factor(s) since quiescent X. laevis nuclei could be stimulated with the rat heart CE. Furthermore, CE from hearts undergoing induced growth had greater activity than extract from control hearts. While cardiac muscle nuclei were not stimulated by heart CE, they showed substantial stimulation by CE from fetal rat liver, which contains a large population of proliferating cells. Stimulation by fetal rat liver was greater with nuclei obtained from hearts undergoing induced growth than from control hearts. Stimulatory factor(s) in CE was distinct from DNA polymerase-α activity, as shown by separation of the two activities on a 5 to 15% glycerol gradient.
Identification Of The Cysteine Protease Amb a x As A Novel Major Allergen From Short Ragweed Pollen (Ambrosia artemisiifolia)
Authors: Philippe Moingeon, Julien Bouley, Maxime Le Mignon, Véronique Baron-Bodo, Véronique Bordas, Laetitia Bussières, Marie-Noëlle Couret, Aurélie Lautrette, Thierry Batard, Rachel Groeme, Henri Chabre, Emmanuel Nony
Journal: Journal of Allergy and Clinical Immunology (2014)
A Randomized Comparison of Sentinel-Node Biopsy with Routine Axillary Dissection in Breast Cancer
Authors: Umberto Veronesi, Giovanni Paganelli, Giuseppe Viale, Alberto Luini, Stefano Zurrida, Viviana Galimberti, Mattia Intra, Paolo Veronesi, Chris Robertson, Patrick Maisonneuve, Giuseppe Renne, Concetta De Cicco, Francesca De Lucia, Roberto Gennari
Journal: New England Journal of Medicine (2003)

Although numerous studies have shown that the status of the sentinel node is an accurate predictor of the status of the axillary nodes in breast cancer, the efficacy and safety of sentinel-node biopsy require validation.From March 1998 to December 1999, we randomly assigned 516 patients with primary breast cancer in whom the tumor was less than or equal to 2 cm in diameter either to sentinel-node biopsy and total axillary dissection (the axillary-dissection group) or to sentinel-node biopsy followed by axillary dissection only if the sentinel node contained metastases (the sentinel-node group).The number of sentinel nodes found was the same in the two groups. A sentinel node was positive in 83 of the 257 patients in the axillary-dissection group (32.3 percent), and in 92 of the 259 patients in the sentinel-node group (35.5 percent). In the axillary-dissection group, the overall accuracy of the sentinel-node status was 96.9 percent, the sensitivity 91.2 percent, and the specificity 100 percent. There was less pain and better arm mobility in the patients who underwent sentinel-node biopsy only than in those who also underwent axillary dissection. There were 15 events associated with breast cancer in the axillary-dissection group and 10 such events in the sentinel-node group. Among the 167 patients who did not undergo axillary dissection, there were no cases of overt axillary metastasis during follow-up.Sentinel-node biopsy is a safe and accurate method of screening the axillary nodes for metastasis in women with a small breast cancer.
Subcutaneous versus intravenous formulation of trastuzumab for HER2-positive early breast cancer: updated results from the phase III HannaH study
Authors: C. Jackisch, S.-B. Kim, V. Semiglazov, B. Melichar, X. Pivot, C. Hillenbach, D. Stroyakovskiy, B.L. Lum, R. Elliott, H.A. Weber, G. Ismael
Journal: Annals of Oncology (2014)
A trial-based cost-effectiveness analysis of letrozole followed by tamoxifen versus tamoxifen followed by letrozole for postmenopausal advanced breast cancer
Authors: J. Karnon, S.R.D. Johnston, T. Jones, A. Glendenning
Journal: Annals of Oncology (2003)

Third-generation aromatase inhibitors are being considered as an alternative to tamoxifen as first-line therapy for advanced breast cancer. These newer therapies are more expensive, and will gain greater acceptance if they can demonstrate cost-effectiveness.Life table analyses are used to compare the costs and benefits [life years gained and quality-adjusted life years (QALYs) gained] of treating postmenopausal women with advanced breast cancer with first-line letrozole (with the option of second-line tamoxifen) compared with first-line tamoxifen (with the option of second-line letrozole). Patient-level data from a large clinical trial describes the effectiveness of the therapy options, clinicians estimate resource usage and utility values are obtained from the literature.The mean cost of providing first- and second-line hormonal therapy is pound 4765 if letrozole is the first-line therapy and pound 3418 if tamoxifen is provided first (a difference of pound 1347). However, patients receiving letrozole as first-line therapy gain an additional 0.228 life years, or 0.158 QALYs. The cost-effectiveness analysis found that first-line hormonal therapy with letrozole gains additional life years at a cost of pound 5917, whilst the cost per additional QALY gained is pound 8514.The strategy of letrozole as first-line hormonal therapy not only provides an opportunity for extending and improving patient's quality of life, but also is highly cost-effective compared with other generally accepted medical treatments.
Induction of Allogeneic Unresponsiveness in Adult Dogs
Authors: F. T. Rapaport, R. J. Bachvaroff, K. Watanabe, H. Hirasawa, N. Mollen, J. W. Ferrebee, D. B. Amos, F. D. Cannon, D. A. Blumenstock
Journal: Journal of Clinical Investigation (1978)

Exposure to supralethal total body irradiation and transplantation of bone marrow from a DLA- and pedigree-identical donor have regularly produced successful engraftment and the establishment of stable long-term chimerism in beagles of the Cooperstown colony. Bone marrow allografts performed in pairs of dogs bearing identical DLA haplotypes derived from different pedigree origins (i.e., different classes of the same haplotype) yielded two different results. Depending upon the particular haplotype pedigree combination used, such transplants either led to long-term chimerism or to failures of engraftment, secondary disease, and death of the recipients (i.e., pedigree-incompatible combinations).
Safety and tolerability of guadecitabine (SGI-110) in patients with myelodysplastic syndrome and acute myeloid leukaemia: a multicentre, randomised, dose-escalation phase 1 study
Authors: Jean-Pierre J Issa, Gail Roboz, David Rizzieri, Elias Jabbour, Wendy Stock, Casey O'Connell, Karen Yee, Raoul Tibes, Elizabeth A Griffiths, Katherine Walsh, Naval Daver, Woonbok Chung, Sue Naim, Pietro Taverna, Aram Oganesian, Yong Hao, James N Lowder, Mohammad Azab, Hagop Kantarjian
Journal: The Lancet Oncology (2015)
The Sweden Cancerome Analysis Network - Breast (SCAN-B) Initiative: a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine
Authors: Lao H Saal, Johan Vallon-Christersson, Jari Häkkinen, Cecilia Hegardt, Dorthe Grabau, Christof Winter, Christian Brueffer, Man-Hung Eric Tang, Christel Reuterswärd, Ralph Schulz, Anna Karlsson, Anna Ehinger, Janne Malina, Jonas Manjer, Martin Malmberg, Christer Larsson, Lisa Rydén, Niklas Loman, Åke Borg
Journal: Genome Medicine (2015)
Anticardiolipin antibodies: occurrence in Behcet's syndrome.
Authors: R G Hull, E N Harris, A E Gharavi, A Tincani, R A Asherson, G Valesini, A M Denman, G Froude, G R Hughes
Journal: Annals of the Rheumatic Diseases (1984)

Anticardiolipin antibodies have recently been described in association with arterial and venous thrombosis, and with neurological symptoms, in connective tissue diseases. In a study of 70 patients with Behçet's syndrome 13 patients had these antibodies. Of these 13 patients eight had a history of either retinal vascular pathology, cerebral infarction, or thrombophlebitis. The association of retinal vascular disease and the presence of anticardiolipin antibodies was statistically significant.
APRIL, a New Ligand of the Tumor Necrosis Factor Family, Stimulates Tumor Cell Growth
Authors: Michael Hahne, Takao Kataoka, Michael Schröter, Kay Hofmann, Martin Irmler, Jean-Luc Bodmer, Pascal Schneider, Tierry Bornand, Nils Holler, Lars E. French, Bernard Sordat, Donata Rimoldi, Jürg Tschopp
Journal: The Journal of Experimental Medicine (1998)

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family designated APRIL (for a proliferation-inducing ligand). Although transcripts of APRIL are of low abundance in normal tissues, high levels of mRNA are detected in transformed cell lines, and in human cancers of colon, thyroid, and lymphoid tissues in vivo. The addition of recombinant APRIL to various tumor cells stimulates their proliferation. Moreover, APRIL-transfected NIH-3T3 cells show an increased rate of tumor growth in nude mice compared with the parental cell line. These findings suggest that APRIL may be implicated in the regulation of tumor cell growth.
The tumor suppressor gene KCTD11 REN is regulated by Sp1 and methylation and its expression is reduced in tumors
Authors: M Michela Mancarelli, Francesca Zazzeroni, Lucia Ciccocioppo, Daria Capece, Agnese Po, Simona Murgo, Raffaello Di Camillo, Christian Rinaldi, Elisabetta Ferretti, Alberto Gulino, Edoardo Alesse
Journal: Molecular Cancer (2010)

Abstract A hallmark of several human cancers is loss of heterozygosity (LOH) of chromosome 17p13. The same chromosomal region is also frequently hypermethylated in cancer. Although loss of 17p13 has been often associated with p53 genetic alteration or Hypermethylated in Cancer 1 ( HIC1 ) gene hypermethylation, other tumor suppressor genes (TSGs) located in this region have critical roles in tumorigenesis. A novel TSG mapping on human chromosome 17p13.2 is KCTD11 REN ( KCTD11 ). We have recently demonstrated that KCTD11 expression is frequently lost in human medulloblastoma (MB), in part by LOH and in part by uncharacterized epigenetic events. Using a panel of human 177 tumor samples and their normal matching samples representing 18 different types of cancer, we show here that the down-regulation of KCTD11 protein level is a specific and a diffusely common event in tumorigenesis. Additionally, in order to characterize the regulatory regions in KCTD11 promoter, we identified a CpG island and several Sp1 binding sites on this promoter, and demonstrated that Sp1 transcription factor and DNA methylation contribute, at least in part, to regulate KCTD11 expression. Our findings identify KCTD11 as a widely down-regulated gene in human cancers, and provide a basis to understand how its expression might be deregulated in tumor cells.
Antibody Light-Chain-Restricted Recognition of the Site of Immune Pressure in the RV144 HIV-1 Vaccine Trial Is Phylogenetically Conserved
Authors: Kevin Wiehe, David Easterhoff, Kan Luo, Nathan I. Nicely, Todd Bradley, Frederick H. Jaeger, S. Moses Dennison, Ruijun Zhang, Krissey E. Lloyd, Christina Stolarchuk, Robert Parks, Laura L. Sutherland, Richard M. Scearce, Lynn Morris, Jaranit Kaewkungwal, Sorachai Nitayaphan, Punnee Pitisuttithum, Supachai Rerks-Ngarm, Faruk Sinangil, Sanjay Phogat, Nelson L. Michael, Jerome H. Kim, Garnett Kelsoe, David C. Montefiori, Georgia D. Tomaras, Mattia Bonsignori, Sampa Santra, Thomas B. Kepler, S. Munir Alam, M. Anthony Moody, Hua-Xin Liao, Barton F. Haynes
Journal: Immunity (2014)
Increased Risk of Hypertension After Gestational Diabetes Mellitus
Authors: Deirdre K. Tobias, Frank B. Hu, John P. Forman, Jorge Chavarro, Cuilin Zhang
Journal: Diabetes Care (2011)

Whether a history of gestational diabetes mellitus (GDM) is associated with an increased risk of hypertension after the index pregnancy is not well established.We investigated the association between GDM and subsequent risk of hypertension after the index pregnancy among 25,305 women who reported at least one singleton pregnancy between 1991 and 2007 in the Nurses' Health Study II.During 16 years of follow-up, GDM developed in 1,414 women (5.6%) and hypertension developed in 3,138. A multivariable Cox proportional hazards model showed women with a history of GDM had a 26% increased risk of developing hypertension compared with those without a history of GDM (hazard ratio 1.26 [95% CI 1.11-1.43]; P=0.0004). These results were independent of pregnancy hypertension or subsequent type 2 diabetes.These results indicate that women with GDM are at a significant increased risk of developing hypertension after the index pregnancy.
Pkm2 Expression Could Predict Resistance to Oxaliplatin Combination Chemotherapy in Patients with Stage Ii/Iii or Metastatic Colorectal Cancer
Authors: Zacharenia Saridaki, Chara Papadaki, Maria Tzardi, Maria Sfakianaki, Georgia Sfakiotaki, George Giagas, Ippokratis Messaritakis, Eleftheria Tsakalaki, Maria Trypaki, Demitris Mavroudis, Vassilis Georgoulias, John Souglakos
Journal: Annals of Oncology (2013)
Immunotherapy with aluminum hydroxide adsorbed insect venom extracts (Alutard SQ): immunologic and clinical results of a prospective study over 3 years
Authors: M. Wyss, T. Scheitlin, B. M. Stadler, B. Wüthrich
Journal: Allergy (1993)

This prospective study over 3 years investigated the safety, immunogenicity, and effectiveness of immunotherapy (IT) with aluminum hydroxide adsorbed insect venom extracts (Alutard SQ, ALK Laboratories) in patients with previous, severe, systemic, IgE-mediated, anaphylactic reactions to Hymenoptera stings. Seventeen patients were treated with honeybee venom (BV), 13 with yellow-jacket venom (YJV), and 5 with both. No severe reactions to IT were noted. Only 3 BV-allergic patients experienced mild systemic reactions of grades I or II (1 per 139 injections) during the increase phase. As for the immunologic data, there was a significant decrease in specific IgE antibodies after 1 year, and a significant increase in specific IgG and IgG4 antibodies on reaching the maintenance dose, with a further rise after 1, 2, and 3 years. Moreover, a significant decrease in anti-IgE autoantibodies was observed in the BV group. Out of the 11 patients that were occasionally restung by the relevant insect (totaling 19 stings in all), only one patient developed mild systemic allergic symptoms after a third sting. In view of these results, we consider IT with aluminum hydroxide adsorbed insect venom extracts to be safe, immunogenic, and effective. The low rate of side-effects may be due to the slow release of the venom in the aluminum hydroxide adsorbed form.
Association Between Allelic Variation of Serotonin Transporter Function and Neuroticism in Anxious Cluster C Personality Disorders
Authors: Christian P. Jacob, A. Strobel, K. Hohenberger, T. Ringel, L. Gutknecht, A. Reif, B. Brocke, K.P. Lesch
Journal: American Journal of Psychiatry (2004)

Association between the low-activity variant of a polymorphism in the transcriptional control region of the serotonin transporter (5-HTTLPR) and neuroticism or harm avoidance was found in several but not all studies. The authors analyzed the influence of 5-HTTLPR variants on personality disorders.Patients with personality disorders (N=320) and healthy volunteers (N=281) were studied with the Revised NEO Personality Inventory and the Tridimensional Personality Questionnaire. All were genotyped for 5-HTTLPR variants.No differences in 5-HTTLPR genotype distribution were detected between patients with cluster B and C personality disorders and comparison subjects. In contrast, among patients with a cluster C diagnosis, carriers of the low-activity short allele of the 5-HTTLPR exhibited higher neuroticism scores than noncarriers.These findings support the notion that there is no general association between the 5-HTTLPR and anxiety-related traits and that differential gene effects and/or gene-by-environment interactions are likely operative in distinct clinical subpopulations.
Characteristics and Outcome of Gastrointestinal Stromal Tumors (Gist): a Single Center Experience Over a Decade
Authors: Dimitrios Tzilves, Ioannis Pilpilidis, Anthia Gatopoulou, Persefoni Xiroy, Georgia Lazaraki, Frinda Patakiouta, Anestis Tarpagos
Journal: Annals of Oncology (2013)
Activated Marrow-Infiltrating Lymphocytes Effectively Target Plasma Cells and Their Clonogenic Precursors
Authors: Kimberly Noonan, William Matsui, Paolo Serafini, Rebecca Carbley, Gladys Tan, Jahan Khalili, Mark Bonyhadi, Hyam Levitsky, Katie Whartenby, Ivan Borrello
Journal: Cancer Research (2005)

Abstract A major limitation of adoptive immunotherapy is the availability of T cells specific for both terminally differentiated tumor cells and their clonogenic precursors. We show here that marrow-infiltrating lymphocytes (MILs) recognize myeloma cells after activation with anti-CD3/CD28 beads with higher frequency than activated peripheral blood lymphocytes from the same patients. Furthermore, activated MILs target both the terminally differentiated CD138+ plasma cells and the myeloma precursor as shown by profound inhibition in a tumor clonogenic assay. The presence of antigen in the marrow microenvironment seems to be important for the maintenance of tumor specificity. Taken together, these results highlight the intrinsic tumor specificity of MILs and describe a novel approach for the generation of tumor-specific T-cell populations suitable for adoptive immunotherapy of multiple myeloma.
Cell-mediated lympholysis of trinitrophenyl-modified autologous lymphocytes. Confirmation of genetic control of response to trinitrophenyl-modified H-2 antigens by the use of anti-H-2 and anti-Ia antibodies.
Authors: A M Schmitt-Verhulst, D H Sachs, G M Shearer
Journal: The Journal of Experimental Medicine (1976)

Splenic lymphocytes from B10.A and B10.D2 mice were sensitized in vitro to trinitrophenyl (TNP)-modified autologous spleen cells. The effector cells generated were assayed in a 51Cr-release assay on TNP-modified syngeneic or congenic spleen target cells. Effector cells from B10.A donors lysed TNP-modified H-2Kk- but not H-2Dd-region products, whereas B10.D2 effectors reacted with modified products of both the H-2Kd and H-2Dd regions. As an independent confirmation that this selective K-end lysis by B10.A effector cells is due to an H-2-linked responder cell defect (4), anti-H-2Kk but not anti-H-2Dd sera were shown to inhibit the lysis of B10.A-TNP targets by B10.A effectors. In contrast, anti-H-2Dd sera inhibited the lysis of B10.A-TNP targets by B10.D2 effectors. Anti-Ia antibodies had no detectable effect on lysis. Anti-TNP-keyhole limpet hemocyanin sera blocked the lysis of TNP-modified targets, irrespective of whether the effector cells were directed against TNP-modified autologous H-2 products or H-2 alloantigens. These results independently verify that B10. A responding lymphocytes do not generate effector cells to TNP-modified H-2Dd products, whereas B10.D2 lymphocytes do (4), and suggest that some TNP groups are sterically close to (or part of) the serologically defined H-2K- and H-2D-region antigens.
Determinants of coronary artery reactivity in premenopausal female cynomolgus monkeys with diet-induced atherosclerosis.
Authors: J K Williams, C A Shively, T B Clarkson
Journal: Circulation (1994)

BACKGROUND The purpose of this study was to identify determinants of coronary artery reactivity among premenopausal female monkeys. Estrogen replacement therapy in postmenopausal females modulates reactivity of atherosclerotic coronary arteries. However, no studies have evaluated the factors that modulate coronary artery reactivity among premenopausal females. METHODS AND RESULTS Twenty-five adult premenopausal female monkeys were fed an atherogenic diet for 32 months. During this time, monkeys were housed in small social groups and determined to be socially dominant (associated with normal ovarian function) or subordinate (associated with impaired ovarian function). After 32 months, coronary artery vasomotor responses to intracoronary acetylcholine, nitroglycerin, and serotonin were assessed by computer-assisted quantitative coronary angiography. Coronary arteries of dominant monkeys dilated (+9 +/- 2%), whereas those of subordinate monkeys constricted (-6 +/- 2%) in response to acetylcholine (P &lt; .05). There was no effect of social status on vascular response to nitroglycerin or serotonin (P &gt; .10). Vascular responses to acetylcholine were independent of social status effects on plasma lipids, blood pressure, and atherosclerosis extent. The correlation between acetylcholine responses and plasma estradiol concentration measured on the day of angiography was r = .7 (P = &lt; .01). Furthermore, dilation occurred only if plasma estradiol concentrations were greater than 60 pg/mL. CONCLUSIONS Psychosocial factors and endogenous estrogen production are important modulators of acetylcholine-mediated dilation of atherosclerotic coronary arteries among premenopausal female monkeys.
Sustained Src Inhibition Results in Signal Transducer and Activator of Transcription 3 (STAT3) Activation and Cancer Cell Survival via Altered Janus-Activated Kinase–STAT3 Binding
Authors: Banibrata Sen, Babita Saigal, Nila Parikh, Gary Gallick, Faye M. Johnson
Journal: Cancer Research (2009)

Locoregional and distant recurrence remains common and usually fatal for patients with advanced head and neck squamous cell carcinoma (HNSCC). One promising molecular target in HNSCC is the Src family kinases (SFK). SFKs can affect cellular proliferation and survival by activating the signal transducer and activator of transcription (STAT) family of transcription factors, especially STAT3. Surprisingly, sustained SFK inhibition resulted in only transient inhibition of STAT3. We investigated the mechanism underlying STAT3 activation and its biological importance. Specific c-Src knockdown with small interfering RNA (siRNA) resulted in STAT3 activation showing specificity, which was inhibited by Janus-activated kinase (JAK; TYK2 and JAK2) depletion with siRNA. Sustained SFK inhibition also resulted in recovered JAK-STAT3 binding and JAK kinase activity after an initial reduction, although JAK phosphorylation paradoxically decreased. To determine the biological significance of STAT3 activation, we combined specific STAT3 depletion with a pharmacologic SFK inhibitor and observed increased cell cycle arrest and apoptosis. Likewise, the addition of STAT3- or JAK-specific siRNA to c-Src-depleted cells enhanced cytotoxicity relative to cells incubated with c-Src siRNA alone. These results show that reactivation of STAT3 after sustained, specific c-Src inhibition is mediated through altered JAK-STAT3 binding and JAK kinase activity and that this compensatory pathway allows for cancer cell survival and proliferation despite durable c-Src inhibition. To our knowledge, this novel feedback pathway has never been described previously. Given that pharmacologic SFK inhibitors are currently being evaluated in clinical trials, these results have potential clinical implications for cancer therapy.