tbuckley/cabot-search huggingface dataset:
Matrix metalloproteinase 8 reduces the invasive, tumorigenic and metastatic potential of breast cancer cells
Authors: Steve Goodison, Virginia Urquidi, Jing Yuan
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2180 

Knowledge of the molecular mechanisms involved in metastatic spread is needed to facilitate advances in prognostic evaluation for individual patients and in the design of therapeutic interventions to inhibit the process. We have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 are spontaneously occurring sublines of the MDA-MB-435 cell breast tumor cell line that exhibit phenotypic differences in growth, invasion, and metastatic efficiency in athymic mice. We have previously reported the overexpression of matrix metalloproteinase 8 (MMP8) in the non-metastatic cell line NM2C5 with respect to its expression in the metastatic M4A4 cell line and that the reduction of MMP8 expression by antisense methodology resulted in increased invasiveness in NM2C5 cells. In the present study the effect of overexpression of different alternatively spliced MMP8 isoforms in the metastatic M4A4 cell line was investigated. In addition to the 467 amino acid (aa) standard MMP8 isoform, at least two other variant forms are expressed in various cell lines. The first variant (444 aa) is characterized by an absence of the signal peptide as a result of the use of a different translation initiation codon. The second MMP 8 variant (368 aa) is the result of a deletion in exon 8 which introduces a frame shift and the truncation of the C-terminus hemopexin domain. The metastatic potential of M4A4 cells engineered to overexpress the standard MMP8 and these variant isoforms was found to be considerably reduced (p<0.05) when compared with the same cells transduced with the respective vector only controls after orthotopic implantation in athymic mice. In addition, the invasive and tumorigenic capabilities of these engineered M4A4 cells were reduced as a result of the expression of the MMP8 variants. Our results are in agreement with the protective role conferred by MMP8 in cancer reported by Balbin et al. in MMP8 deficient mice and open new avenues for the study of the mechanisms through which MMP8 isoforms influence the biological activities of their substrates. This study also underscores the need of specific anti-MMP therapeutic approaches in cancer.
Abstract 16132: Effectiveness of Adaptive Servo-Ventilation Therapy in NYHA-IV Heart Failure Patients
Authors: Toshimitsu Kato, Noriaki Takama, Masahiko Kurabayashi
Journal: Circulation (2014)

Introduction: Adaptive servo-ventilation (ASV) therapy is considered clinically beneficial to patients with heart failure (HF). On the other hands, large proportion of patients who are scheduled for ASV therapy are serious HF, and they are resistant to medication therapy. Some of them do not respond to ASV therapy. We aimed to identify the effectiveness of ASV therapy in serious HF patients. Methods: After medical therapy was optimized, a 6-months follow up study was conducted of 95 patients with NYHAIV HF. The patients were classified into two groups, which were ASV therapy group (56 patients, 74.9 ± 10.1 years, 31 male) and non-ASV therapy group (39 patients, 78.5 ± 8.6 years, 24 male). The incidence of fatal cardiovascular events including death from progression of HF, fatal cardiac arrhythmias was tracked. Results: No significant differences were observed between two groups with regard to age, gender, body mass index, drug therapy, cardiovascular risk factors, left ventricular ejection fraction (ASV t...
Risk Factors Associated with Incident Cataracts and Cataract Surgery in the Age-Related Eye Disease Study (AREDS)
Authors: Jessica R. Chang, Euna Koo, Elvira Agrón, Joelle Hallak, Traci Clemons, Dimitri Azar, Robert D. Sperduto, Frederick L. Ferris, Emily Y. Chew
Journal: Ophthalmology (2011)
Abstract 16260: Aspirin-Responsive Platelet Genes Are Associated With Platelet Function and Cardiovascular Events
Authors: Sunil Suchindran, Tiffany Himmel, Thomas L Ortel, Richard C Becker, William E Kraus, L K Newby, Geoffrey S Ginsburg, Deepak Voora
Journal: Circulation (2014)

Background: Aspirin prevents myocardial infarction (MI); the pathways with which aspirin interacts are not fully described. We hypothesized that genes that changed in response to aspirin exposure would be associated with platelet function and death/MI. Methods: Discovery (healthy volunteers; n=53) and Validation (diabetic patients; n=45) cohorts were exposed to aspirin 325mg/day. Before and after aspirin exposure, we measured platelet function by aggregometry and gene/platelet protein expression by whole blood RNA microarray analysis and unbiased proteomics of purified platelet protein, respectively. Gene Set Enrichment Analysis (GSEA) identified gene sets that changed in response to aspirin. Paired t-tests and regression were used to test individual genes and proteins for changes in expression with aspirin or association with platelet function, respectively. Cox regression models tested gene sets in aggregate using the 1st principal component of gene expression for association with death/MI in patients (n =638) using RNA collected at cardiac catheterization. Results: In the discovery cohort we identified 25 gene sets that changed in response to aspirin (family wise error rate [FWER] &lt; 0.05). Of these, we chose to follow up on one set of 43 genes because it represented abundant platelet genes. This gene set was down regulated in the discovery and validation cohorts (FWER p = 0.01 and 0.04, respectively). We identified 4 of 43 genes in the platelet protein dataset; the expression of 3 changed (p &lt; 0.03) in response to aspirin and was associated (p &lt; 0.01) with platelet function after accounting for aspirin. The aggregate expression of this platelet gene set was associated with death/MI (p = 0.03) with the majority of genes associated with increased risk. Analysis of individual genes in this gene set identified several (HLA-E, H3F3A, GNAS, FTH1, TUBA4A, OAZ1, FLNA) that were significantly (p &lt; 0.05) down-regulated by aspirin and also associated with an increased risk of death/MI. Conclusion: By using aspirin as a probe to uncover novel biology we identified a set of aspirin-responsive platelet genes associated with an increased risk of cardiovascular events. These findings may help to explain the effects of aspirin on preventing MI.
Abstract 8811: Pheochromocytoma Cardiomyopathy: The Extreme Effect of Catecholamines on the Heart
Authors: Rajat M Gupta, Akshay S Desai
Journal: Circulation (2011)

A previously healthy 19-year-old man was admitted with nausea, vomiting and labile blood pressures after several months of headaches and palpitations. Though normotensive on presentation, his blood pressure rose to 240/160 mmHg after administration of IV metoclopramide. He then developed dyspnea, acute pulmonary edema, and became hypotensive. Echocardiogram revealed an LV ejection fraction of 10% without cavity dilation. Coronary angiography revealed no coronary artery disease, and ventriculography revealed no regional wall motion abnormalities or apical ballooning. Given the concern for myocarditis, an RV endomyocardial biopsy was performed, which revealed necrotic myocytes, but no inflammatory infiltrate. CT scan of the abdomen revealed a 4.0 x 3.5 cm mass within the right adrenal gland and plasma normetanephrine levels were markedly elevated at 28.8 nmol/L. In the context of a presumptive diagnosis of pheochromocytoma complicated by catecholaminergic cardiomyopathy, plans were made for surgical resection of the tumor following alpha-adrenergic blockade. Continued hypotension prompted urgent implantation of a percutaneous ventricular assist device (pVAD). With pVAD support, hemodynamics improved over 2 weeks, serial echocardiograms showed improvement in LV ejection fraction to 60%, and laparoscopic removal of the adrenal mass was safely undertaken. Pathology confirmed a pheochromocytoma. Pheochromocytoma-induced cardiogenic shock is a rare syndrome described after adrenergic storm triggered by mechanical compression, tumor hemorrhage, or administration of dopaminergic agonists, such as metoclopromide in this case. The pathophysiology of acute myocardial stunning during catecholamine surge remains unclear. Postulated mechanisms include coronary vasospasm, direct toxic effects of catecholamines on cardiomyocytes, and a newly proposed hypothesis of Gi-receptor-coupled catecholamine signaling (stimulus trafficking). Our patient illustrates that the inhibitory effects of catecholamine excess on myocardial function may be reversible with early clinical recognition, aggressive hemodynamic support, appropriate pre-operative preparation, and surgical resection by a specialized team.
Current status and future prospects of parenteral insulin regimens, strategies and delivery systems for diabetes treatment1Abbreviations: AIA, antiinsulin antibody; CAPD, continuous ambulatory dialysis; CSII, continuous subcutaneous insulin infusion; DCCT, diabetes control complications trial; FIR, far infrared radiation; GLP1, glucagon-like peptide 1; GH, growth hormone; HbA1c, glycated hemoglobin; IDDM, insulin-dependent diabetes mellitus; IGF1, insulin-like growth factor 1; i.p., …
Authors: Nathalie Jeandidier, Sophie Boivin
Journal: Advanced Drug Delivery Reviews (1999)
Statistics notes: Sample size in cluster randomisation
Authors: S. M Kerry, J M. Bland
Journal: BMJ (1998)

<h3>Abstract</h3> Techniques for estimating sample size for randomised trials are well established,12 but most texts do not discuss sample size for trials which randomise groups (clusters) of people rather than individuals. For example, in a study of different preparations to control head lice all children in the same class were allocated to receive the same preparation. This was done to avoid contaminating the treatment groups through contact with control children in the same class.3 The children in the class cannot be considered independent of one another and the analysis should take this into account.45 There will be some loss of power due to randomising by cluster rather than individual and this should be reflected in the sample size calculations. Here we describe sample size calculations for a cluster randomised trial.
Abstract P2-08-01: Autoimmunity in breast carcinogenesis. A new paradigm
Authors: Félix Fernández Madrid, Marie-Claire Maroun, Leonard Lipovich, Larry Tait, Azadeh Stark, Richard Zarbo, Lisa Polin, Dhananjay Chitale
Journal: Cancer Research (2015)

Abstract The B cell response in breast cancer [BC] may have a tumor-promoting effect. The objective of this work was to demonstrate that TAAs and cytokines inflict autoimmune damage to the breast creating a chronic inflammatory milieu that promotes BC progression Methods: The DCIS.com nude mouse xenograft model of BC was treated with rituximab and dexamethasone. Immunoscreening of a cDNA library, PCR, and sequence determination. Immunohistochemistry [IHC] for inflammatory cytokines, immunoglobulins and complement and the TUNEL assay. Results: Deposition of immunoglobulins and complement was shown on breast epithelial and stromal cells and the involvement of IL-4, IL-6, IL-17, TNF-alpha and NFkB was demonstrated by IHC staining. We identified autoantibodies recognizing multiple human breast epithelial and stromal antigens and the Fc and V regions of immunoglobulins. Rituximab and dexamethasone treatment markedly modified the macroscopic and microscopic appearance of BC and the pattern of cytokine deposition, induced increase in vascularity, marked stromal hypertrophy and massive debulking of the tumor by drastically reducing the tumor mass through apoptosis. Conclusions: These results suggest that autoantibody- and cytokine-mediated autoimmune damage, triggered by TAAs creates a chronic inflammatory milieu with generation of pro-inflammatory and tumor promoting signals supporting BC progression. The dramatic results of the treatment of the xenograft model with rituximab and dexamethasone illustrate the potential of treating BC as a chronic rheumatic autoimmune disease. The demonstration of a major role of autoimmunity in BC progression may have a transformative impact on prevention, diagnosis and treatment of BC. Citation Format: Félix Fernández Madrid, Marie-Claire Maroun, Leonard Lipovich, Larry Tait, Azadeh Stark, Richard Zarbo, Lisa Polin, Dhananjay Chitale. Autoimmunity in breast carcinogenesis. A new paradigm [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-08-01.
Improving Access to Kidney Transplantation
Authors: Lauren M. Kucirka, Tanjala S. Purnell, Dorry L. Segev
Journal: JAMA (2015)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
872. AAV 1 and 8 Have Higher Efficacy Than AAV 2 in Correction of Hyperbilirubinemia in the Gunn Rat, the Animal Model for the Metabolic Liver Dissorder Crigler-Najjar Syndrome
Authors: Piter J. Bosma, Berry de Jong, Norbert Looije, Cindy Kunne, Conny T. Bakker, Jurgen Seppen
Journal: Molecular Therapy (2004)
Economic Development Key to Healthier World
Authors: David Banta
Journal: JAMA (2002)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Koro: proposed classification for DSM-IV
Authors: R L Bernstein, A C Gaw
Journal: American Journal of Psychiatry (1990)

Koro, a culture-specific disorder consisting of complaints of genital retraction and fear of death associated with genital retraction, has been recognized in Asian cultures in single cases and in epidemic proportions. Koro has been described in non-Asian patients as well, leading to debate concerning the true nature of the syndrome. The authors review past attempts to define and classify koro and present a classification for DSM-IV that they believe could be used to classify other culture-bound syndromes as well.
Abstract 4010: MicroRNA regulator of NMI: implications for breast cancer
Authors: Hawley C. Pruitt, Jack W. Rostas III, Brandon J. Metge, Daniel J. Devine, Sarah K. Bailey, Lalita A. Shevde, Rajeev Samant
Journal: Cancer Research (2014)

Abstract Recent investigations by our laboratory have demonstrated that NMI expression is down-regulated in patient breast tumors, especially those displaying invasive/metastatic features. In breast cancer and melanoma cell lines, restored expression of NMI suppresses tumor growth. Furthermore, NMI negatively impacts TGFβ-driven epithelial-mesenchymal-transition (EMT) and alsometastatic invasion of breast cancer. Thus the mechanisms that regulate NMI expression are of potential interest to understand the etiology of breast tumor progression, invasion, metastasis and to identify potentially novel therapeutic targets. MicroRNAs are critical regulators of gene expression. MicroRNA target prediction searches revealed that the NMI transcript could be targeted by the miR-29 family, a group of miRNAs with multiple roles in diverse cancer types. We hypothesized that miR-29 will negatively regulate NMI expression. Luciferase reporter assays using pMIR-REPORTTM confirmed the projected interaction of miR-29 in the seed region of the 3′ UTR of NMI. Manipulation of miR-29 levels in breast cancer cells by overexpression or silencing showed its inverse relationship with NMI expression. Invasive mesenchymal-like breast cancer cell lines showed elevated endogenous levels of miR-29 relative to tumorigenic/non-metastatic (epithelial like) breast cancer cell lines. Moreover, transient overexpression of miR-29 enhanced breast cancer cell invasion as measured by modified Boyden chamber assay and silencing miR-29 using anti-miRs decreased invasion. Investigations on the impact of miR-29 modulation on EMT revealed that increasing miR-29 levels in epithelial-like breast cancer cell lines caused 3D morphological changes indicative of invasive mesenchymal-like growth, while decreasing miR-29 levels from mesenchymal-like cell types using anti-miRs reversed the phenotype and the growth pattern resembled acinar structures. The significance of our observation was realized when we compared RNA isolated from patient derived breast cancer tumors and compared with RNA from matched adjacent normal breast specimens. Analysis using the McNemar's test showed a strong, inverse relationship between the expression of NMI and the miR-29. We contend that aberrant miR-29 expression may account for reduced NMI in some invasive breast cancers. Citation Format: Hawley C. Pruitt, Jack W. Rostas III, Brandon J. Metge, Daniel J. Devine, Sarah K. Bailey, Lalita A. Shevde, Rajeev Samant. MicroRNA regulator of NMI: implications for breast cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4010. doi:10.1158/1538-7445.AM2014-4010
Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder
Authors: Christoph U. Correll, Johan Detraux, Jan De Lepeleire, Marc De Hert
Journal: World Psychiatry (2015)

People with severe mental illness have a considerably shorter lifespan than the general population. This excess mortality is mainly due to physical illness. Next to mental illness-related factors, unhealthy lifestyle, and disparities in health care access and utilization, psychotropic medications can contribute to the risk of physical morbidity and mortality. We systematically reviewed the effects of antipsychotics, antidepressants and mood stabilizers on physical health outcomes in people with schizophrenia, depression and bipolar disorder. Updating and expanding our prior systematic review published in this journal, we searched MEDLINE (November 2009 - November 2014), combining the MeSH terms of major physical disease categories (and/or relevant diseases within these categories) with schizophrenia, major depressive disorder and bipolar disorder, and the three major psychotropic classes which received regulatory approval for these disorders, i.e., antipsychotics, antidepressants and mood stabilizers. We gave precedence to results from (systematic) reviews and meta-analyses wherever possible. Antipsychotics, and to a more restricted degree antidepressants and mood stabilizers, are associated with an increased risk for several physical diseases, including obesity, dyslipidemia, diabetes mellitus, thyroid disorders, hyponatremia; cardiovascular, respiratory tract, gastrointestinal, haematological, musculoskeletal and renal diseases, as well as movement and seizure disorders. Higher dosages, polypharmacy, and treatment of vulnerable (e.g., old or young) individuals are associated with greater absolute (elderly) and relative (youth) risk for most of these physical diseases. To what degree medication-specific and patient-specific risk factors interact, and how adverse outcomes can be minimized, allowing patients to derive maximum benefits from these medications, requires adequate clinical attention and further research.
302. Engineered Zinc Finger Transcription Factors: A Platform for Therapeutic Gene Regulation with Exquisite Specificity
Authors: Dmitry Guschin, Steve Zhang, Lei Zhang, Siyuan Tan, Victor Bartsevich, Casey Case, Edward Rebar, Philip Gregory
Journal: Molecular Therapy (2004)

A challenge of modern medicine is the development of effective yet highly specific drugs. To this end, we are developing artificial zinc finger protein transcription factors (ZFP TFs) as direct therapeutic agents for the treatment of disease. Here we show that ZFP TFs can be designed to activate or repress a wide range of clinically relevant genes, including Phospholamban, a regulator of heart contractivity, Chk2, a kinase with a role in DNA damage pathway and P2X7, a ligand-gated channel. Moreover, using these examples and the Affymetrix GeneChipR platform we show that these ZFP TFs regulate the targeted gene with exceptional and often singular specificity genome wide, despite the complexity of mammalian genome. This exquisite specificity is independent of both gene target and species, while occurring in the context of maximal efficacy. This combination of potency and specificity supports the clinical potential of ZFP TF technology.
New Drug for Erectile Dysfunction Boon for Many, "Viagravation" for Some
Authors: L Lamberg
Journal: JAMA (1998)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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