tbuckley/cabot-search huggingface dataset:
Stromelysin-3 plays a contributory role in epithelial-mesenchymal transition (EMT) and is a downstream target of Wnt1 signaling
Authors: Laurence Blavier, Zhe Zhou, Alisa Lazaryev, Gregory M. Shackleford, Yves A. Declerck
Journal: Cancer Research (2006)

4353   Matrix metalloproteinases (MMPs) have been generally considered to play a role in later stages of tumor progression. However there has been evidence that they may contribute to earlier stages of malignant transformation. The Wnt signaling transduction pathway plays a critical role in development and also in the pathogenesis of many epithelial cancers. Here we have used Wnt1-induced epithelial mesenchymal transition (EMT) in C57MG murine mammary epithelial cells to study  in vitro  the role of MMPs in this early step of malignant progression. Transfection of C57MG cells with Wnt1 promoted EMT, the translocation of β-catenin from the cell membrane to the cytoplasm and the nucleus, and the proliferation and motility of Wnt1 expressing cells. At the same time, we observed an increased expression of stromelysin-1 (MMP-3) in the absence of changes in the expression of MMP-2, MMP-9 or tissue inhibitors of metalloproteinase TIMP-1 or TIMP-2. The effect of Wnt1 on EMT, proliferation and migration was inhibited in the presence of recombinant TIMP-2 or AG3340, a synthetic MMP inhibitor, suggesting that MMP-3 plays a contributory role in Wnt1-induced EMT. Interestingly, treatment of these cells with AG3340 also decreased MMP-3 expression, suggesting that MMP-3 is also a downstream target of Wnt1 signaling. To test this possibility C57MG cells expressing Wnt1 were transfected with pGL2-SL-1-Luc plasmid containing the full-length murine MMP-3 promoter driving a luciferase reporter gene. We observed a 4.5 fold increase in promoter activity in C57MG cells expressing Wnt1 compared with C57MG parent cells. The murine MMP-3 promoter has two T-cell factor binding elements (TCF/LCF) located at position −331 and −1043. We observed an increase in luciferase activity upon mutation of the distal TCF/LCF binding element (position −1043) and a decrease in luciferase activity upon mutation of the proximal TCF/LCF binding element (−331), suggesting an inhibitory and stimulatory effect respectively. These results suggest that MMP-3 is a direct transcriptional target of the Wnt/β-catenin signaling pathway, and plays a contributory role in Wnt1-mediated EMT.
p53 gene deletion predicts for poor survival and non-response to therapy with purine analogs in chronic B-cell leukemias
Authors: H Dohner, K Fischer, M Bentz, K Hansen, A Benner, G Cabot, D Diehl, R Schlenk, J Coy, S Stilgenbauer, M Volkmann, P R Galle, A Poustka, W Hunstein, P Lichter
Journal: Blood (1995)
Abstract 17406: Inhibition of MicroRNA-133a Expression is Associated with Poor Growth Response of Vascular Smooth Muscle Cells to Insulin-Like Growth Factor-1 in Apolipoprotein-E Deficient Mice
Authors: Song Gao, Michael Wassler, Yangxin Li, Lulu Zhang, Harnath Shelat, Yong-Jian Geng
Journal: Circulation (2011)

Background and Objective. Alternations in growth and differentiation of vascular smooth muscle cells (SMC) contribute to the pathogenesis of atherosclerosis. Certain microRNAs (miR) have been shown to regulate cardiovascular cell growth and differentiation. For instance, miR-133a plays a role in cardiac muscle development. However, it is largely unknown if miR-133a affects SMC proliferation in atherosclerosis. This study was designed to analyze miR-133a expression and SMC growth in atherosclerosis and to explore if insulin growth factor (IGF)-1 receptor is involved in the miR-133a effect on SMC growth. Methods and Results. qRT-PCR analysis of total RNA extracted revealed lower levels of miR133a in SMC cultured from apolipoprotein E-null (apoE -/- ) mice than those in wild-type C57BL/6J (WT). Interestingly, IGF-1R mRNA levels were lower in the ApoE -/- cells. Immunofluorescence for IGF-1R was positive in both the sections of WT and ApoE -/- mice aorta but the latter displayed weaker signals. In cultured WT SMCs, IGF-IR protein expression decreased by about 66% after incubation with miR-133a inhibitor. In contrast, IGF-IR levels increased by almost 3-fold when the cells were treated with miR-133a precursor. Growth curves showed that SMC proliferation was attenuated with miR-133a inhibitor(Fig.1). The decreased SMC proliferation was caused by poor response to IGF-1 as addition of IGF-1 did not increase SMC numbers in the cultures. However, incubation with miR-133a precursor increased proliferation of WT SMC by 25% and ApoE -/- SMC by 10%. Conclusions. Down-regulation of miR-133a expression with miR-133a inhibitor decreases IGF-1R expression and inhibits the growth of WT SMCs but to a less degree in Apo -/- SMC. In contrast, overexpression of miR-133a increases IGF-1R expression and promotes the IGF-1 derived the SMC growth. The data suggest that miR-133a may participate in regulation of SMC growth in atherosclerotic vascular tissue.
Alcohol and Drug Use, History
Authors: Dan Malleck
Journal: JAMA (2004)

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
Abstract 9424: Caloric Restriction Augments Cardiomyocyte Autophagy to Mitigate Postinfarction Cardiac Remodeling and Heart Failure
Authors: Takatomo Watanabe, Genzou Takemura, Hiromitsu Kanamori, Akiko Tsujimoto, Goto Kazuko, Atsushi Ogino, Toshiaki Takeyama, Tomonori Kawaguchi, Kentaro Morishita, Hisayoshi Fujiwara, Takako Fujiwara, Shinya Minatoguchi
Journal: Circulation (2011)

We previously reported that cardiomyocyte autophagy is an innate mechanism that protects against progression of postinfarction cardiac remodeling. In the present study, we examined effect of caloric restriction (CR), a potent inducer of autophagy, on post infarction cardiac remodeling. Myocardial infarction (MI) was induced in mice by ligating the left coronary artery. After one week of MI, mice were randomly divided into the following four groups. The control group was fed ad libitum (100%). Others were fed restricted diet: 80%, 60%, and 40% of the total calorie which was taken by control mice. The water was provided ad libitum. Three weeks later, we performed echocardiography and catheter to evaluate the left ventricular (LV) function. There was no mouse that died through the period. The body weight was decreased in CR groups (post/pre ratio: 1.08±0.01 in control, 0.83±0.01 in 80% CR, 0.76±0.01 in 60% CR, 0.70±0.01 in 40% CR, p&lt;0.001). However, there was no difference in heart/body weight ratio. The dilatation and hypofunction of the LV were apparent in the control group: left ventricular diastolic dimension (LVDd) = 4.9±0.1 mm; left ventricular ejection fraction (LVEF) = 27±3.3%; and dP/dT = 4677±277 mmHg/s. However, both dilatation and hypofunction were significantly mitigated in groups undergoing CR: in 80%, 60%, and 40% CR, respectively, LVDd = 4.0±0.1 mm, 3.4±0.2 mm and 4.0±0.1 mm; LVEF = 36±2.8%, 51±4.3% and 43±1.5%; and dP/dT = 6849±221 mmHg/s, 7758±638 mmHg/s and 6923±553 mmHg/s, among which the 60% CR group showed the strongest therapeutic effect on postinfarction cardiac remodeling (control vs. 60% CR: p&lt;0.001). Cardiomyocyte autophagy was markedly activated in CR groups as evidenced by the overexpressed microtubule-associated protein 1 light chain 3-II (LC3-II) and specific ultrastructural findings including autophagosome formation. In conclusion, caloric restriction enhances cardiomyocyte autophagy and mitigates postinfarction cardiac remodeling and dysfunction; the optimal caloric restriction is suggested to be 60%. These findings suggest an important clinical implication that a dietary protocol can be a preventive strategy against progression of postinfarction left ventricular remodeling and heart failure.
Abstract 17907: Challenges of Anticoagulation during Cardiopulmonary Bypass in Children: Impact of Low Antithrombin Levels
Authors: Cedric Manlhiot, Colleen E Gruenwald, Helen M Holtby, Leonardo R Brandao, Glen S Van Arsdell, Brian W McCrindle
Journal: Circulation (2014)

Introduction: Heparin-based anticoagulation in children is challenging as they have a high prevalence of heparin resistance. Antithrombin, one of the main natural anticoagulant inhibitors that potentiate heparin anticoagulation activity, might be a critical component of heparin response and anticoagulation effectiveness. Objectives: Determine the impact of antithrombin levels on anticoagulation (heparin sensitivity and effectiveness) during cardiopulmonary bypass (CPB) in children &lt;1 year old. Methods: Secondary analysis of a randomized controlled trial of individualized vs weight based heparin management in 90 infants &lt;1-year-old undergoing cardiac surgery. All analyses combined both patient groups and were used linear regression models. Results: As expected, older patients had higher blood antithrombin levels (relative increase of 16±6% for patients &gt;6 months old vs. those &lt;6 month old, p=0.009). Response to heparin, reflected by change in anti-Xa levels from baseline after the initial heparin bolus (a laboratory measure of heparin sensitivity), was highest in patients with higher baseline antithrombin circulating levels (top tier: +0.94(0.16) U/ml per 100U/kg heparin vs. middle tier: +0.89(0.19) U/ml vs. lowest tier: +0.77(0.20) U/ml, p&lt;0.001). Those patients with very low antithrombin levels during CPB (&lt;0.35U/ml) had much greater heparin requirements (+165(30) U/kg/hr representing an increase of 243%, p&lt;0.001) indicating greater heparin resistance. Insufficient anticoagulation on bypass (as measured by end of bypass anti-Xa level) was associated with higher clotting potential, reflected by higher plasma levels of thrombin-antithrombin complexes (+4.8(2.4) ng/ml per anti-Xa U/ml, p=0.05), and prothrombin activation fragment 1.2 (+85(32) pg/ml per anti-Xa U/ml, p=0.008). Moreover, lower circulating antithrombin level was associated with increased D-dimer levels after CPB (+53(25) ng/ml per 0.1 U/ml antithrombin, p=0.03). Conclusions: Low antithrombin level is associated with resistance to heparin and decreased anticoagulation activity, ultimately leading to lower ability to suppress thrombin generation during CPB. Antithrombin supplementation may potentially individualize and improve anticoagulation.
P0088 : Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I -1518 reduces bacterial translocation in rats treated with CCL4
Authors: G. Soriano, E. Sánchez, J.C. Nieto, S. Vidal, F.J. Sancho, P. Sancho-Bru, B. Mirelis, H. Corominola, C. Juárez, C. Guarner
Journal: Journal of Hepatology (2015)
Interleukin-8 is regulated by a Src/STAT3 pathway in pancreatic adenocarcinoma cells that is NF-κB independent
Authors: José G. Trevino, Michael J. Gray, Justin M. Summy, Steffan T. Nawrocki, Douglas B. Evans, Paul J. Chiao, Stephanie S. Watowich, Gary E. Gallick
Journal: Cancer Research (2006)

4835  Human pancreatic tumors often overexpress the angiogenesis-promoting factor Interleukin-8 (IL-8), due, in part, to increased activity of the transcription factor NF-κB. Recently, we have demonstrated that Src, constitutively active in >70% of pancreatic tumors, also deregulates IL-8 expression. This study examined whether Src-mediated IL-8 expression is NF-κB-dependent or-independent. The effects of Src activity on IL-8 expression in pancreatic tumor cell lines were determined by pharmacologic inhibition of Src and creation of stable clones with reduced Src activity by siRNA technology. The role of STAT3 in IL-8 expression was assessed by transient transfection of dominant negative and activated STAT3 constructs, followed by determination of IL-8 promoter activity using reporter constructs and IL-8 expression by ELISA. Finally, the effects of Src inhibition on NF-κB transcriptional activity and NF-κB p65 nuclear translocation were assessed. We demonstrate that reduced expression or activity of Src significantly decreased IL-8 expression (P
Measures used in study are hard to interpret
Authors: A M Mander, S C Leeson
Journal: BMJ (1996)

EDITOR,—Stuart J Anderson and colleagues' study of the predictors of neonatal encephalopathy in full term infants1 is timely in view of changes and practices in Britain and trends in litigation. It is worrying, however, that serious problems with interpretation are known to arise with several of the measures of intrapartum events used in the study to indicate birth asphyxia and subsequent neonatal encephalopathy. …
Abstract 12: Differences in the Rate of Bystander CPR Based on Location of Cardiac Arrest in the Out-of-Hospital Setting
Authors: Robert E O'Connor, Ross E Megargel, Diane McGinnis-Hainsworth, Melissa Bollinger, David Zamara
Journal: Circulation (2006)

Purpose: Bystander CPR is one of the crucial links in the chain of survival from cardiac arrest. We conducted this study to determine how often bystander CPR was performed in the out-of-hospital se...
Abstract 3225: Inhibition of microRNAas762, 762+ 21, and microRNAs762+31, Differentiates Cardiac Stem Cells into Cardiomyocytes by Activation of TGF{beta}III and Activin A Receptors Pathways
Authors: Edilamar M de Oliveira, Aftab Ahmad, Dafina Ibrani, Yao Liang Tang, M. I Phillips
Journal: Circulation (2009)
Abstract A73: De-convoluting therapeutic resistance in a pancreatic cancer model: Pharmacogenomic evaluation of intratumoral clonal heterogeneity
Authors: Eveline E. Vietsch, John K. Simmons, Ivana Peran, Marianne Stenstra, Beverly A. Mock, Anton Wellstein
Journal: Cancer Research (2015)

Abstract Background: The duration of therapeutic response in pancreatic adenocarcinoma to both targeted therapies and conventional chemotherapeutics is abysmal, greatly contributing to the 5-year survival rate of this disease remaining in the single digits. Given the high proliferative rate of these tumors, and the frequent occurrence of mutations in genes critical for maintaining genomic integrity, we hypothesized that rapid therapeutic resistance may largely be the consequence of intratumoral heterogeneity present at the onset of therapy. Materials and Methods: To address this question, an integrated genomic and pharmacologic survey was performed on a panel of clonal cell lines generated from a tumor arising in a Kras/Trp53 mutant mouse model (p48-Cre; LSL-KrasG12D; LSL-Trp53R172H). Results: All lines screened maintained tumorigenicity upon allografting, and exhibited metastatic capacity. Whole exome sequencing confirmed that 94% of driver mutations found in the clonal lines were also present in the tumor. Importantly, each clonal line contains unique passenger mutations. Exposure of these lines to conventional chemotherapeutics in vitro (i.e. gemcitabine, doxorubicin, and vincristine) showed high variance in sensitivity, with 10-fold ranges of IC50s among the lines. Screening of the clonal cell lines with a kinase inhibitor library of 200 compounds, showed distinct vulnerabilities to targeted pathways between the lines. Gene expression profiling and pathway analysis highlighted variation in critical cellular pathways between the lines. Conclusions: Our results in this model system implicate ab initio drug resistance in these heterogeneous tumors as a major contributor to the poor therapeutic outcomes in this disease. This applies to conventional chemotherapy as well as targeted inhibitors. Citation Format: Eveline E. Vietsch, John K. Simmons, Ivana Peran, Marianne Stenstra, Beverly A. Mock, Anton Wellstein. De-convoluting therapeutic resistance in a pancreatic cancer model: Pharmacogenomic evaluation of intratumoral clonal heterogeneity. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr A73.
Donor CD3 Chimerism After Allogeneic Transplantation Predicts Probability Of Relapse For Patients Treated For Acute Myelogenous Leukemia (AML), Acute Lymphoblastic Leukemia (ALL), and Non-Hodkgin's Lymphoma (NHL)
Authors: Arpita P Gandhi, Michele L. Donato, Themba Nyirenda, David H. Vesole, Andrew L Pecora, Stuart Goldberg, Andre Goy, Tatyana Feldman, Anthony R. Mato, Pritish K. Bhattacharyya, Melissa Baker, Phyllis McKiernan, Brenda Diaz, Scott D Rowley
Journal: Blood (2013)
The paired-box domain of the fusion oncoprotein PAX3-FKHR suppresses its oncogenic activity
Authors: Shujuan J. Xia, Frederic G. Barr
Journal: Cancer Research (2005)

Proc Amer Assoc Cancer Res, Volume 46, 2005

6121 

Alveolar rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer associated with the skeletal muscle lineage. A characteristic feature of ARMS is a specific 2;13 chromosomal translocation, resulting in a chimeric protein PAX3-FKHR. Our previous studies showed that the fusion protein transformed NIH3T3 cells at low expression level, but suppressed cell growth at higher expression levels (Oncogene, 23:6864, 2004). This transformation was evidenced by soft agar colony growth but not focus formation. To further study the transforming activity of this oncogene, an estrogen inducible system was produced by linking PAX3-FKHR to a modified estrogen receptor ligand binding domain (ER), and subcloning the construct into the pBabe retroviral vector. In contrast to our previous studies with the pK1 retroviral vector, the expression level of PAX3-FKHR-ER from the pBabe vector was much lower in NIH3T3 cells, and at this level, PAX3-FKHR-ER did not cause growth suppression. To further explore the functions of the two distinct DNA-binding domains, inactivating mutations were introduced into the paired-box or the homeodomain of PAX3-FKHR-ER using site-directed mutagenesis. In the soft agar assay of anchorage-independence as one measure of cellular transformation, the ligand tamoxifen induced a moderate level of transformation in cells transduced with wild-type PAX3-FKHR-ER but was unable to induce transformation in cells transduced with the homeodomain mutant, consistent with our previous findings. However, in the absence of any growth suppression, the ligand induced enhanced transformation in cells transduced with the paired box mutant. More interestingly, only the paired-box mutation form of PAX3-FKHR-ER induced foci in the focus formation assay, another transformation assay that assesses cell contact inhibition. Therefore, PAX3-FKHR mutated in the paired-box domain is a more potent oncogenic form compared to wild-type in both soft agar and focus assays. Based on these findings, we hypothesize that the paired-box domain exerts an inhibitory effect on the oncogenic behavior of PAX3-FKHR by regulating downstream target gene(s) that interfere with the cellular process. We further hypothesize that events that interfere with PAX3-FKHR paired box function, either by protein-protein interaction or direct mutation, will promote tumorigenesis by increasing its oncogenic activity and decreasing its growth suppressive activity.
Abstract 17998: Continuous Warm Perfusion Reduces Renal Injury During Norwood Operation
Authors: James M Hammel, Haili Lang, Kim F Duncan
Journal: Circulation (2011)

Objectives: Perfusion approaches for Norwood include hypothermic circulatory arrest and selective cerebral perfusion. Both techniques result in cold renal ischemia (CRI). Canulation of both the innominate artery and the descending aorta allows maintenance of continuous warm perfusion (CWP) to the kidney and the entire body during arch reconstruction. Renal dysfunction often complicates recovery after complex neonatal cardiac surgery. This review was undertaken to assess the effect of perfusion technique, CRI or CWP, on postoperative renal function. Methods: Records of 46 consecutive neonates undergoing Norwood since 2004 were reviewed. The Acute Dialysis Quality Initiative Group RIFLE criteria for renal injury and failure were applied. Results: 17 patients underwent Norwood with CWP, 29 with CRI. Both median bypass time and median crossclamp time were significantly shorter in CWP than CRI (100 v. 189 min, p = 0.005 and 26 v. 68 min, p &lt; 0.001). Creatinine change from baseline was significantly less in CWP than CRI at 24 and 48 hours (1.19 +/- 0.24 v. 1.58 +/- 0.61, p = 0.02; and 1.58 +/- 0.60 v. 1.16 +/- 0.28, p = 0.01)(see Chart). 1 of 17 CWP patients had renal injury by urine output criteria at 24 hours, compared to 7 of 29 CRI patients (p=0.01). 0 of 17 CWP had renal injury by creatinine change criteria, and 2 of 17 had risk of renal dysfunction, versus 6 of 29 and 12 of 29 CRI respectively (p = 0.006 and p = 0.003). Median fluid balance at 24 hours was +121 ml. for CWP vs. +252 ml for CRI. Renal dysfunction eventually resolved in all patients. Conclusions: Patients undergoing Norwood with continuous warm perfusion of the entire body had less transient renal injury. This was reflected in less early positive fluid balance. Early postoperative renal dysfunction can be avoided through this alternative perfusion technique.
Poor housing continues to affect health adversely
Authors: Susan Mayor
Journal: BMJ (2003)

Poor housing continues to adversely affect the health of some of the most vulnerable groups of people living in England, warned a report published this week by the BMA.

The report examined available evidence in relation to health and housing. It found that children living in bed and breakfast accommodation (temporary housing, often with relatively poor cooking and washing facilities) were at increased risk of behavioural problems, stress, poor sleep, infections, and gastrointestinal problems.

The health of the many elderly people who live alone in old, damp, and cold homes was also at risk, said the report.
Abstract 106: Increasing CPR during Out-of-hospital Ventricular Fibrillation Arrest: Survival Implications of Guideline Changes
Authors: Thomas D Rea, Michael Helbock, Stephen Perry, Don Cloyd, Mickey S Eisenberg
Journal: Circulation (2006)

Background: The most recent resuscitation guidelines have sought to improve the interface between defibrillation and CPR. However, the survival implications of these changes are unknown. A year pri...