tbuckley/cabot-search huggingface dataset:
Functional Genomics Identifies ABCC3 as a Mediator of Taxane Resistance in HER2-Amplified Breast Cancer
Authors: Carol O'Brien, Guy Cavet, Ajay Pandita, Xiaolan Hu, Lauren Haydu, Sankar Mohan, Karen Toy, Celina Sanchez Rivers, Zora Modrusan, Lukas C. Amler, Mark R. Lackner
Journal: Cancer Research (2008)

Abstract Breast cancer is a heterogeneous disease with distinct molecular subtypes characterized by differential response to targeted and chemotherapeutic agents. Enhanced understanding of the genetic alterations characteristic of different subtypes is needed to pave the way for more personalized administration of therapeutic agents. We have taken a functional genomics approach using a well-characterized panel of breast cancer cell lines to identify putative biomarkers of resistance to antimitotic agents such as paclitaxel and monomethyl-auristatin-E (MMAE). In vitro studies revealed a striking difference in sensitivity to these agents between cell lines from different subtypes, with basal-like cell lines being significantly more sensitive to both agents than luminal or HER2-amplified cell lines. Genome-wide association studies using copy number data from Affymetrix single nucleotide polymorphism arrays identified amplification of the chromosome 17q21 region as being highly associated with resistance to both paclitaxel and MMAE. An unbiased approach consisting of RNA interference and high content analysis was used to show that amplification and concomitant overexpression of the gene encoding the ABCC3 drug transporter is responsible for conferring in vitro resistance to paclitaxel and MMAE. We also show that amplification of ABCC3 is present in primary breast tumors and that it occurs predominantly in HER2-amplified and luminal tumors, and we report on development of a specific fluorescence in situ hybridization assay that may have utility as a predictive biomarker of taxane resistance in breast cancer. [Cancer Res 2008;68(13):5380–9]
Antigen-Induced Bronchial Anaphylaxis in Actively Sensitized SD Rats.
Authors: Magnus Dahlbäck
Journal: Allergy (1981)

Bronchial anaphylactic reactions, estimated as increase in intratracheal pressure, were precipitated by intravenous injections of antigen into actively sensitized SD rats. The degree of bronchial reactivity was found to depend on both the challenge dose and the immunization dose of antigen; therefore the course of the capacity to respond was recorded as a function of these variables. The degree of the bronchial anaphylactic response could be reduced by pretreatment with disodium cromoglycate, terbutaline or a new anti-allergic xanthine derivative, D 4026, in some groups of animals. The efficacy of each agent was found to depend on the dose of antigen used for sensitization and for provocation of the bronchial reaction rather than on the strength of the response. Taken together, the data suggest that more than one type of homocytotropic antibody mediates bronchial anaphylactic reactivity in the SD rat.
Impact of Mammographic Screening on Breast Cancer Diagnosis
Authors: W. P. MCWHORTER, H. J. EYRE
Journal: JNCI Journal of the National Cancer Institute (1990)

Journal Article Impact of Mammographic Screening on Breast Cancer Diagnosis Get access WILLIAM P. MCWHORTER, WILLIAM P. MCWHORTER Division of Hematology-Oncology University of Utah School of Medicine Salt Lake CityUT 84132 Search for other works by this author on: Oxford Academic PubMed Google Scholar HARMON J. EYRE HARMON J. EYRE Division of Hematology-Oncology University of Utah School of Medicine Salt Lake CityUT 84132 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 82, Issue 2, 17 January 1990, Pages 153–154, https://doi.org/10.1093/jnci/82.2.153 Published: 17 January 1990
High-dose therapy followed by autologous peripheral-blood stem-cell transplantation for patients with Hodgkin's disease and non-Hodgkin's lymphoma using unprimed and granulocyte colony-stimulating factor-mobilized peripheral-blood stem cells.
Authors: A Nademanee, I Sniecinski, G M Schmidt, A C Dagis, M R O'Donnell, D S Snyder, P M Parker, A S Stein, E P Smith, A Molina
Journal: Journal of Clinical Oncology (1994)

PURPOSE To evaluate (1) the effect of granulocyte colony-stimulating factor (G-CSF) on peripheral-blood stem-cell (PBSC) mobilization; (2) the rate of hematopoietic recovery after G-CSF-mobilized PBSC transplantation; and (3) the outcome of high-dose myeloablative therapy and PBSC transplantation in patients with relapsed or refractory lymphoma. PATIENTS AND METHODS Ninety-five patients with lymphoma underwent high-dose therapy followed by PBSC transplant in three sequentially treated cohorts of patients in a nonrandomized study. The first 30 patients received nonmobilized PBSCs (unprimed) without G-CSF after transplant, the next 26 patients received PBSC that were mobilized with G-CSF 5 micrograms/kg/d (primed-5) plus G-CSF after transplant, and the last 39 patients received PBSC mobilized by G-CSF 10 micrograms/kg/d (primed-10) plus G-CSF after transplant. The conditioning regimen consisted of fractionated total-body irradiation (FTBI) 12 Gy in combination with etoposide 60 mg/kg and cyclophosphamide 100 mg/kg. Patients with prior radiotherapy received carmustine (BCNU) 450 mg/m2 instead of FTBI. RESULTS The use of G-CSF-mobilized PBSCs in combination with G-CSF posttransplant resulted in a significantly accelerated time to recovery of both granulocyte and platelet when compared with the unprimed group. The median number of days to an absolute granulocyte count (ANC) of greater than 0.5 x 10(9)/L was 10 days for G-CSF primed versus 20 days for the unprimed (P = .0001). The median days to platelet transfusion independence was 16 and 31 days (P = .0001) for the G-CSF primed and unprimed, respectively. There were also significant reductions in the number of platelet (P = .02) and RBC transfusions (P = .006) for the G-CSF primed. Multivariate analysis of prognostic factors identified CD34+ cell dose as the only additional factor predicting engraftment. Sixty-nine patients are alive at a median follow-up of 15.9 months (range, 7.4 to 63.7). The cumulative probability of 2-year disease-free survival is 59% (95% confidence interval [CI], 36% to 79%) and 39% (95% CI 25% to 55%) for patients with Hodgkin's disease and non-Hodgkin's lymphoma, respectively. CONCLUSION The use of G-CSF-mobilized PBSC after high-dose myeloablative therapy resulted in a rapid, complete, and sustained hematopoietic recovery. Disease-free survival over 2 years can be achieved in some patients with relapsed lymphoma after high-dose therapy and PBSC transplantation. However, longer follow-up is required to confirm the curability of this approach.
Detection and Localization of Proteinuria by Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using MS325
Authors: Yantian Zhang, Peter L. Choyke, Huiyan Lu, Hideko Takahashi, Roslyn B. Mannon, Xiaojie Zhang, Hani Marcos, King C.P. Li, Jeffrey B. Kopp
Journal: Journal of the American Society of Nephrology (2005)

After renal transplantation, persistent glomerular disease affecting the native kidneys typically causes albuminuria, at least for a period of time, making it difficult to determine in a noninvasive fashion whether proteinuria originates in the native kidneys or the renal allograft. To address this problem, dynamic contrast-enhanced magnetic resonance imaging (MRI) using gadolinium (Gd)-based albumin-bound blood pool contrast agent (MS325) to localize proteinuria was investigated. Glomerular proteinuria was induced in Sprague-Dawley rats by intravenous injection of puromycin aminonucleoside (PAN), whereas control rats received physiologic saline vehicle. Both groups of animals underwent a 40-min dynamic contrast-enhanced MRI using radio frequency spoiled gradient echo imaging sequence after injection of Gd-labeled MS325. Contrast uptake and clearance curves for cortex and medulla were determined from acquired MR images. Compared with controls, proteinuric rats exhibited significantly lower elimination rate constants. The use of gadopentetate dimeglumine (Gd-DTPA) as a contrast agent showed smaller and less specific differences between proteinuric and control groups. In rats with one proteinuric kidney (PAN-treated) and one normal kidney (transplanted from a normal rat), MRI using MS325 was able to differentiate between the two kidneys. The results suggest that MRI with an albumin-bound blood pool contrast agent may be a useful noninvasive way to localize proteinuria. If this technique can be successfully applied in human patients, it may allow for the localization of proteinuria after kidney transplant and thereby provide a noninvasive way to detect disease affecting the renal allograft.
Reactivation of tuberculosis and vitamin D deficiency: the contribution of diet and exposure to sunlight
Authors: A Sita-Lumsden, G Lapthorn, R Swaminathan, H J Milburn
Journal: Thorax (2007)

As well as its role in the regulation of calcium metabolism, vitamin D is an immunoregulatory hormone. Epidemiological evidence also suggests a link between vitamin D deficiency and tuberculosis (TB). A study was undertaken to examine serum vitamin D concentrations before treatment in patients with active TB and their contacts from the same ethnic and social background and to investigate the relative contributions of diet and sunlight exposure.
Influence of metronidazole resistance on efficacy of quadruple therapy for <i>Helicobacter pylori</i> eradication
Authors: R W M van der Hulst, A van der Ende, A Homan, P Roorda, J Dankert, G N J Tytgat
Journal: Gut (1998)

Metronidazole-containing eradication therapies are less effective for metronidazole resistant Helicobacter pylori. Although early data suggested improvement of the efficacy of bismuth triple therapy after the addition of acid suppressives, these findings were based on studies with small numbers of patients, incomplete post-eradication follow up, or omission of pretreatment susceptibility testing.To study the efficacy of quadruple therapy in the Amsterdam area, where the efficacy of bismuth triple therapy has been proved to be affected by metronidazole resistance.Eighty two consecutive dyspeptic H pylori positive patients with either metronidazole susceptible (group I) or metronidazole resistant H pylori strains (group II) received quadruple therapy for one week: omeprazole 20 mg twice daily; colloidal bismuth subcitrate 120 mg four times a day; tetracycline 500 mg four times a day; metronidazole 500 mg three times a day. Susceptibility to metronidazole was determined by the E-test.Intention to treat analysis showed that H pylori infection had been cured in 42/43 patients (98%) in group I and 32/39 patients (82%) in group II (p = 0.02).The efficacy of quadruple therapy is significantly impaired in patients infected with metronidazole resistant H pylori. Therefore a non-metronidazole-containing regimen should preferably be used in areas known to have a high prevalence of pretreatment metronidazole resistance.
Extensive Subepicardial Fibrosis in a Patient With Apical Hypertrophic Cardiomyopathy With Persistent ST-Segment Elevation Simulating Acute Myocardial Infarction
Authors: Jong-Won Ha, Byoung-Wook Choi, Se-Joong Rim, Seok-Min Kang, Yangsoo Jang, Namsik Chung, Won-Heum Shim, Seung-Yun Cho
Journal: Circulation (2005)
Sex and Racial/Ethnic Differences in Cardiovascular Disease Risk Factor Treatment and Control Among Individuals With Diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Ginger J. Winston, R. Graham Barr, Olveen Carrasquillo, Alain G. Bertoni, Steven Shea
Journal: Diabetes Care (2009)

OBJECTIVE To examine sex and racial/ethnic differences in cardiovascular risk factor treatment and control among individuals with diabetes in the Multi-Ethnic Study of Atherosclerosis (MESA). RESEARCH DESIGN AND METHODS This study was an observational study examining mean levels of cardiovascular risk factors and proportion of subjects achieving treatment goals. RESULTS The sample included 926 individuals with diabetes. Compared with men, women were 9% less likely to achieve LDL cholesterol &amp;lt;130 mg/dl (adjusted prevalence ratio 0.91 [0.83–0.99]) and systolic blood pressure (SBP) &amp;lt;130 mmHg (adjusted prevalence ratio 0.91 [0.85–0.98]). These differences diminished over time. A lower percentage of women used aspirin (23 vs. 33%; P &amp;lt; 0.001). African American and Hispanic women had higher mean levels of SBP and lower prevalence of aspirin use than non-Hispanic white women. CONCLUSIONS Women with diabetes had unfavorable cardiovascular risk factor profiles compared with men. African American and Hispanic women had less favorable profiles than non-Hispanic white women.
Herbal Medicine in Europe — Relaxing Regulatory Standards
Authors: Peter A G M De Smet
Journal: New England Journal of Medicine (2005)

Herbal medicine is big — and relatively mainstream — business in Europe: in 2003, European countries spent almost $5 billion (at manufacturers' prices to wholesalers) on over-the-counter herbal medicines. But not all European countries have embraced herbal treatments with equal warmth. Germany and France are indisputably in the lead in over-the-counter sales (see graph), and they have also had noteworthy markets for prescription herbal preparations. In 2003, German health insurance paid $283 million in reimbursements for prescribed ginkgo, St. John's wort, mistletoe, saw palmetto, ivy, hawthorn, stinging nettle root, myrtol, phytosterols, and cucurbita, and in 2002, French health insurance paid . . .
Differential effects of angiotensin II and transforming growth factor beta on the production of heparan sulfate proteoglycan by mesangial cells in vitro.
Authors: N F van Det, J T Tamsma, J van den Born, N A Verhagen, L P van den Heuvel, C W Löwik, J H Berden, J A Bruijn, M R Daha, F J van der Woude
Journal: Journal of the American Society of Nephrology (1996)

This study approaches the question of whether angiotensin II (AngII) and transforming growth factor beta (TGF-beta) are important mediators for mesangial heparan sulfate proteoglycan (HSPG) production. This might explain the beneficial effects of angiotensin-converting enzyme inhibitors observed in several kidney diseases independent from their hemodynamic effects. Metabolic-labeling studies revealed that AngII induced a decrease of HSPG synthesis with decreases in N-sulfation of the glycosaminoglycan side chains. ELISA measurements with a heparan sulfate (HS)-specific monoclonal antibody confirmed that AngII decreased HS production. AngII increased TGF-beta production in a dose-dependent fashion. Specific mRNA for the large basement membrane HSPG (perlecan) decreased, whereas mRNA for TGF-beta increased after incubation with AngII. Blockade of the Subtype 1 Ang-II receptor (ATR1) reversed both the effects of AngII on HSPG and TGF-beta production. Coincubation of the mesangial cells with neutralizing antibodies against TGF-beta significantly reduced the production of HS as compared with control and AngII. These results indicate that the decrease in HS synthesis induced by AngII is not mediated by an increase in TGF-beta, but on the contrary, the increase in TGF-beta partially counteracts the inhibition of HS production by AngII. Considering the important role of HSPG in maintaining the glomerular charge barrier, cell proliferation, and matrix interaction, downregulation of the production of this molecule by increased local AngII concentrations could have important consequences, such as albuminuria and matrix expansion.
Alpha-fetoprotein-thymidine kinase–luciferase knockin mice: A novel model for dual modality longitudinal imaging of tumorigenesis in liver
Authors: Xincheng Lu, Hong Guo, Joseph Molter, Hui Miao, Lizabeth Gerber, Yiduo Hu, Ellen L. Barnes, Hannes Vogel, Zhenghong Lee, Guangbin Luo, Bingcheng Wang
Journal: Journal of Hepatology (2010)
Impact of Infarct-Related Artery Flow on QT Dynamicity in Patients Undergoing Direct Percutaneous Coronary Intervention for Acute Myocardial Infarction
Authors: Hendrik Bonnemeier, Uwe K.H. Wiegand, Frank Bode, Franz Hartmann, Volkhard Kurowski, Hugo A. Katus, Gert Richardt
Journal: Circulation (2003)

Complete coronary artery reperfusion in acute myocardial infarction (AMI) has been shown to significantly improve survival. Electrical stability may be the decisive mechanism for this beneficial effect. Because electrical stability is largely dependent on ventricular repolarization, we sought to determine the impact of a modern reperfusion strategy (ie, direct percutaneous coronary intervention [PCI]) on QT dynamicity in AMI and examined its association with infarct-related artery flow.We prospectively investigated QT dynamicity in 128 patients undergoing direct PCI for a first AMI. Slopes and correlation coefficients of the linear QT/RR regression were determined in the time interval before reperfusion, within the initial hour after reperfusion, and within the remaining recording period from Holter ECG recordings, which were initiated on admission. Subgroup analysis based on TIMI 3 (n=100) and TIMI 2 (n=28) flow after PCI revealed no significant differences in QT/RR slope before PCI (0.145+/-0.12 versus 0.160+/-0.19,P=NS). After PCI, QT/RR slopes increased only in the TIMI 2 subgroup (P<0.05). In TIMI 2 patients, QT/RR slopes were significantly steeper in the hour after PCI and in the remaining recording period, respectively (0.155+/-0.12 versus 0.192+/-0.15,P<0.05, and 0.159+/-0.10 versus 0.210+/-0.17,P<0.01).Alterations of QT dynamicity in patients with incomplete reperfusion may suggest an altered electrical restitution, potentially providing a substrate for serious ventricular arrhythmias. Thus, our findings offer new insights into mechanisms by which complete reperfusion may affect electrical stability.
Sarcolemmal Versus Mitochondrial ATP-Sensitive K <sup>+</sup> Channels and Myocardial Preconditioning
Authors: Garrett J. Gross, Ryan M. Fryer
Journal: Circulation Research (1999)

Abstract —Ischemic preconditioning (IPC) is a phenomenon in which single or multiple brief periods of ischemia have been shown to protect the heart against a more prolonged ischemic insult, the result of which is a marked reduction in myocardial infarct size, severity of stunning, or incidence of cardiac arrhythmias. Although a number of substances and signaling pathways have been proposed to be involved in mediating the cardioprotective effect of IPC, the overwhelming majority of evidence suggests that the ATP-sensitive potassium channel (K ATP channel) is an important component of this phenomenon and may serve as the end effector in this process. Initially, it was hypothesized that the surface or sarcolemmal K ATP (sarc K ATP ) channel mediated protection observed after IPC; however, subsequent evidence suggested that the recently identified mitochondrial K ATP channel (mito K ATP ) may be the potassium channel mediating IPC-induced cardioprotection. In this review, evidence will be presented supporting a role for either the sarc K ATP or the mito K ATP in IPC and potential mechanisms by which opening these channels may produce cardioprotection; additionally, we will address important questions that still need to be investigated to define the role of the sarc or mito K ATP channel, or both, in cardiac pathophysiology.
An integrated database of genes responsive to the Myc oncogenic transcription factor: identification of direct genomic targets
Authors: Karen I Zeller, Anil G Jegga, Bruce J Aronow, Kathryn A O'Donnell, Chi V Dang
Journal: Genome biology (2003)

We report a database of genes responsive to the Myc oncogenic transcription factor. The database Myc Target Gene prioritizes candidate target genes according to experimental evidence and clusters responsive genes into functional groups. We coupled the prioritization of target genes with phylogenetic sequence comparisons to predict c-Myc target binding sites, which are in turn validated by chromatin immunoprecipitation assays. This database is essential for the understanding of the genetic regulatory networks underlying the genesis of cancers.
Regulation of pleitropic effect of TRAIL on RAFLS by TRAIL-R1 and -R2
Authors: R Audo, A Bruyer, B Combe, M Hahne, J Morel
Journal: Annals of the Rheumatic Diseases (2010)

Rationale Induction of apoptosis in fibroblast-like synoviocytes (FLS) has been proposed as a therapeutic approach. Tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been described as a pro-apoptotic factor on rheumatoid arthritis FLS (RAFLS) and suggested as a potential drug. We have previously shown that exposure to TRAIL induces apoptosis only in a portion of RAFLS. In the surviving cells, TRAIL induced …
Long-lasting skin allograft tolerance in adult mice induced across fully allogeneic (multimajor H-2 plus multiminor histocompatibility) antigen barriers by a tolerance-inducing method using cyclophosphamide.
Authors: H Mayumi, R A Good
Journal: The Journal of Experimental Medicine (1989)

A new method of cyclophosphamide (CP)-induced skin allograft tolerance in mice that can regularly overcome fully allogeneic (major H-2 plus non-H-2) antigen barriers in mice has been established. The components of the method are intravenous or intraperitoneal administration of 50-100 micrograms of anti-Thy-1.2 mAb on day -1, intravenous injection of 90 x 10(6) allogeneic spleen cells mixed with 30 x 10(6) allogeneic bone marrow cells from the same donor on day 0, and intraperitoneal injection of 200 mg/kg CP on day 2. In each of four fully allogeneic donor----recipient combinations, including C3H/HeJ (C3H; H-2k)----C57BL/6J(B6; H-2b), B6----C3H, BALB/cByJ (BALB; H-2d)----B6, and BALB----C3H, long-lasting survival of skin allografts was induced in most of the recipient mice. The specific tolerant state induced was dependent on the doses of the antibody and bone marrow cells used. The optimal timing of CP treatment to induce tolerance was found to be 1-3 d after the stimulating cell injection. Treatment with the anti-Thy-1.2 antibody together with CP on day 2 after the cell injection on day 0 also induced profound tolerance. In the B6 mice made tolerant of C3H with antibody, C3H spleen cells plus C3H bone marrow cells, and then CP, a minimal degree of stable mixed chimerism was established and the antitolerogen (C3H) immune responses examined here, including delayed footpad reaction (DFR), CTL activity, and capacity for antibody production against donor-strain antigens were abrogated in a tolerogen-specific manner. From cell transfer experiments, the mechanism of tolerance could be largely attributed to reduction of effector T cells reactive against the tolerogen, and strong suppressive influences that might prolong skin allograft survival directly were not detected in the tolerant mice. Moreover, pretreatment with anti-Thy-1.2 antibody or anti-L3T4 (CD4) antibody was more effective than pretreatment with anti-Lyt-1 (CD5) antibody or anti-Lyt-2 (CD8) antibody as an initial step in tolerance induction. These results suggest that permanent tolerance to fully allogeneic skin grafts may be induced because antibody given before the stimulating cell injection reduces the number of reactive T cells in the recipient mice. This antibody treatment may facilitate an antigen-stimulated destruction of responding and thus proliferating cells with CP by preventing a possibly less proliferative, more rapid maturation of reactive T cells or by destroying residual effector T cells.(ABSTRACT TRUNCATED AT 400 WORDS)