tbuckley/cabot-search huggingface dataset:
Abstract 4053: Formin-binding protein-17 (FBP17) is a target of p53 and promotes invadopodia formation in breast cancer cells
Authors: Harish Chander, Kathleen Watts, Justin Pogmore, Peter Truesdell, Colin Brien, Andrew W B Craig
Journal: Cancer Research (2014)

Abstract Invadopodia are extracellular matrix (ECM)-degrading structures that promote tissue invasion and metastasis of tumor cells. A family of adaptor proteins with F-BAR and SH3 domains, including FBP17 and Toca-1, have been identified as key scaffolds for recruiting actin regulatory proteins (eg. Cdc42, formins, N-WASP, dynamin) to promote formation of invadopodia in bladder and breast cancers, respectively. In this study, we investigated the potential role of FBP17 in breast cancer models. We observed FBP17 expression in normal breast epithelial cells (MCF10A), and at higher levels in basal breast cancer cell lines (MDA-MB-231) compared to luminal cell lines. Since basal breast cancers frequently harbor mutations in tumor suppressor p53, we tested whether wild-type (WT) p53 regulates expression of FBP17, which may explain higher expression in basal breast cancers. Camptothecin (CPT) treatment of WT p53-expressing breast cancer cells (MCF-7, DU4475) led to a dose dependent reduction in FBP17 mRNA and protein levels, and this was inversely correlated with p53 levels or its target p21WAF1. The downregulation of FBP17 was also observed using Nutlin-3, an Mdm2 inhibitor, indicating that WT p53 activation by multiple methods causes a rapid downregulation of FBP17. Currently we are testing whether this is a direct or indirect effect of p53 on FBP17 gene expression. As expected, FBP17 formed complexes with actin regulatory proteins (dynamin, cortactin, Arp2/3) that accumulate and promote invadopodia formation in MDA-MB-231 cells. Stable silencing of FBP17 in these cells led to a significant reduction in ECM degradation. This is consistent with FBP17 promoting invadopodia formation. Tumor xenograft models are in progress to determine whether FBP17 also promotes tumor metastasis. FBP17 expression levels in human breast tumors are currently being tested to determine whether altered expression occurs in molecular subtypes with frequent mutations in p53 (HER2, basal) and in their metastases. Overall, these results are consistent with FBP17 participating in cancer cell invasion, and supports further studies of its role in cancer metastasis. Citation Format: Harish Chander, Kathleen Watts, Justin Pogmore, Peter Truesdell, Colin Brien, Andrew W B Craig. Formin-binding protein-17 (FBP17) is a target of p53 and promotes invadopodia formation in breast cancer cells. [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 4053. doi:10.1158/1538-7445.AM2014-4053
Estimating Prognosis for Nursing Home Residents With Advanced Dementia
Authors: Baldomero Alvarez-Fernández
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 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
Aquagenic palmoplantar keratoderma: a new sign of cystic fibrosis?
Authors: R. Phillips
Journal: British Journal of Dermatology (2010)

Funding sources: none. Conflicts of interest: none declared. Madam, Garçon‐Michel et al.1 have recently described their experience of detecting aquagenic palmoplantar keratoderma (APPK) in 40% of 27 patients with cystic fibrosis. These data are interesting although no control group was tested. However, some elements of the article are not consistent with previously published reports. The authors use the phrase ‘…a new sign of cystic fibrosis?’ in their title and state that ‘We believe that APPK should be considered a sign of cystic fibrosis’. These statements ignore the references given within their own article and others that demonstrate that aquagenic skin wrinkling has been clearly described by multiple authors as a sign of cystic fibrosis over several decades and is recognized as such in a major textbook.2 The statement by Garçon‐Michel et al. that ‘this study is the first to determine the frequency of APPK among patients with cystic fibrosis…’ is incorrect. Berk et al.3 (referenced by Garçon‐Michel et al.) in 2009 described a considerably larger study looking at the same question in more detail. The frequency and extent of aquagenic palmoplantar wrinkling was measured and compared with controls and the authors provided a detailed description of the range of behaviours that might be expected when palms from patients with cystic fibrosis are immersed in water. The interest by Garçon‐Michel et al. and others in this area is welcome in that it will undoubtedly increase recognition of the link between aquagenic skin wrinkling and both cystic fibrosis and the carrier state for cystic fibrosis.4
Myelodysplastic Syndromes
Authors: Peter L. Greenberg, Eyal Attar, John M. Bennett, Clara D. Bloomfield, Carlos M. De Castro, H. Joachim Deeg, James M. Foran, Karin Gaensler, Guillermo Garcia-Manero, Steven D. Gore, David Head, Rami Komrokji, Lori J. Maness, Michael Millenson, Stephen D. Nimer, Margaret R. O'Donnell, Mark A. Schroeder, Paul J. Shami, Richard M. Stone, James E. Thompson, Peter Westervelt
Journal: Journal of the National Comprehensive Cancer Network (2011)

OverviewThe myelodysplastic syndromes (MDS) represent myeloid clonal hemopathies with relatively heterogeneous spectrums of presentation.The major clinical problems in these disorders are morbidities caused by cytopenias and the potential for MDS to evolve into acute myeloid leukemia (AML).In the general population, MDS occur in 5 per 100,000 people.However, among individuals older than 70 years, the incidence increases to between 22 and 45 per 100,000 and increases further with age.Managing MDS is complicated by the generally advanced age of the patients (median ages, 65-70 years), attendant nonhematologic comorbidities, and relative inability to tolerate certain intensive forms of therapy among older patients.In addition,
Depression and Cardiovascular Health Care Costs Among Women With Suspected Myocardial Ischemia
Authors: Thomas Rutledge, Viola Vaccarino, B. Delia Johnson, Vera Bittner, Marian B. Olson, Sarah E. Linke, Carol E. Cornell, Wafia Eteiba, David S. Sheps, Jennifer Francis, David S. Krantz, C. Noel Bairey Merz, Susmita Parashar, Eileen Handberg, Diane A. Vido, Leslee J. Shaw
Journal: Journal of the American College of Cardiology (2009)
Abstract 18070: Disparities in Advanced Heart Failure Therapy
Authors: Khalil Murad, Samit S Roy, Nonye Harcourt, Monica Colvin
Journal: Circulation (2014)

Background and Objective: Disparities in healthcare delivery are increasingly recognized. In this study, we explored disparities based on gender, race, age, region, and hospital type, in receiving advanced heart failure therapies (AHFT) defined as mechanical circulatory support (MCS) and heart transplantation (HT). Methods: Using data from the Nationwide Inpatient Sample (NIS), the largest all-payer inpatient health care database in the United States, we identified all hospitalizations between 2005-2011 for patients 18-85 years old, with the diagnosis of congestive heart failure, cardiomyopathy, or cardiogenic shock, and with no known contraindications to AHFT. Multivariate logistic regression analysis was used to determine the likelihood of receiving AHFT based on gender (men versus women), race (White versus Black, Hispanic, or others), age (≤50 versus 51-70 or ≥71 years old), hospital type (teaching versus non teaching), and geographic region (West versus Northeast, Mid-west, or South). Results: A total of 3,789,875 hospitalizations met our inclusion criteria, of which 3,769 (0.1%) patients received AHFT: 1,923 (51.0%) received MCS and 1,846 (49.0%) received HT. The following were associated with lower likelihood of receiving AHFT (table 1): female gender, non-white race, older age, non-teaching hospital, and Midwest, Northeast or South geographical region. Conclusion: Gender, race, age and regional disparities exist in the delivery of AHFT therapy. As the population of patients with end-stage heart failure continues to grow, effective public health research and policies are needed to identify the sources of disparities and to ensure equity in delivering AHFT.
Abstract 19748: CD39-associated SNP and Secondary Cardiovascular Events
Authors: Burcu Gul, Jessica T Delaney, Yanna Song, Erica A Bowton, Cara B Sutcliffe, Elena Chepurko, Tatiana Novitskaya, Joshua C Denny, Frank E Harrell, Quinn S Wells, John H Cleator, Richard J Gumina
Journal: Circulation (2014)

Introduction: CD39 (ectonucleoside triphosphate diphosphohydrolase) is a nucleotidase expressed on endothelial cells, vascular smooth muscles cells, leukocytes, and platelets. CD39 plays a key role in vascular homeostasis, hydrolyzing extracellular ATP or ADP to AMP. Prior work has demonstrated that the genotype at the single nucleotide polymorphism (SNP) rs10748643 correlates with CD39 expression on HapMap lymphocytes (GG: high, GA: intermediate, AA: baseline). Hypothesis: The aim of this study was to determine if an association exists between the rs10748643 genotype and secondary cardiovascular events. Methods: Subjects treated with placement of an intracoronary stent and on clopidogrel therapy for coronary artery disease were identified in the BioVU DNA repository that links DNA to Synthetic Derivative, a de-identified electronic health record. Selection of the study population was based on a combination of ICD 9th edition, Current Procedural Terminology codes, laboratory values, and natural language processing in physician notes. “Case” or “control” status was assigned depending on recurrence of a secondary cardiovascular event (myocardial infarction, revascularization and/or death) within two years. Genotyping for rs10748643 was performed using TaqMan. Results: The study population included 189 cases and 379 controls, with comparable demographics. There were 47 MIs, 14 deaths, and 166 revascularizations. We compared the composite outcomes of MI and/or death or MI, death and/or revascularization. We found no difference in the composite end-point of MI, death and revascularization, however the GG-genotype at rs10748443 was associated with an increase in the composite end-point of MI and/or death (HR GG:AA: 3.82 95% CI 1.10 - 13.29; P=0.039). Conclusions: The GG genotype, was associated with an increased incidence of the composite end-point of myocardial infarction and death in patients who received intracoronary stents for coronary artery disease and were treated with clopidogrel. This is the first study to demonstrate an association of a CD39-associated SNP with human cardiac pathology. Confirmatory studies are underway in a larger cohort.
Infectious Diseases: A Modern Treatise of Infectious Processes.
Authors: [edited by] Paul D. Hoeprich, M. Colin Jordan
Journal: Annals of Internal Medicine (1984)

Infectious diseases: A modern treatise of infectious processes , Infectious diseases: A modern treatise of infectious processes , کتابخانه مرکزی دانشگاه علوم پزشکی تهران
Radio: Raging hormones miss the target
Authors: H. Jacobs
Journal: BMJ (1999)

Raging hormones , BBC Radio 4, Tuesdays at 9.30am, 15 June to 13 July

Iaccept that you need a catchy title for a series like this, but hormones don't actually rage—they circulate, very gently. On the other hand, and here I speak from experience, endocrinologists often rage. Their patients sometimes rage as well, but the hormones that cause the commonest type of endocrine rage—premenstrual tension—don't feature in this series at all. Such considerations made me wonder how interesting a molecule based, rather than an illness based or physiology based, series would be—not very, I'm afraid.

It was primarily the missed opportunities that spoiled the series for me. The first programme introduced listeners to the idea that adrenaline underlies the “flight or fight” response to danger. However, some intriguing research into postsurgical pain revealed that blood adrenaline concentrations were highest in the patients who were psychologically most relaxed and who felt the least pain—a paradoxical finding to be sure. The ad hoc …
Abstract 912: P21-activated kinase 4 (PAK4) as a predictive marker for gemcitabine in pancreatic cancer cell line
Authors: Sung Ung Moon, Jin Won Kim, Ji Hea Sung, Mi Hyun Kang, Hyun Chang, Jeong Ok Lee, Yu Jung Kim, Keun Wook Lee, Jee Hyun Kim, Soo Mee Bang, Jong Seok Lee
Journal: Cancer Research (2014)

Abstract Pancreatic cancer is a highly lethal disease. Although gemcitabine is activelyused in pancreatic cancer, modest activity and relativeresistanceare revealed.P21-activated kinases(PAKs) are involved in cytoskeletal reorganization, gene transcription, cellproliferation and survival, and oncogenic transformation.The gene amplification and protein overexpression of PAK1 and PAK4were reported in pancreatic cancer, which were associated with K-ras mutation, MUC13 and Smad4. Therefore, we hypothesized that PAKs could predict the drug-sensitivity of gemcitabine in pancreatic cancer and could be a therapeutic target. Using cell viability assay of human pancreatic cancer cell lines (Capan1, Capan2, MIA-paca2, PANC1, Aspc1, SNU213, SNU410) for gemcitabine, Capan-2, PANC-1 and SNU-410 cell lines was identifiedas resistant cell lines for gemcitabine. Through western blots of molecules related with down-steam pathway and drug-sensitivity, higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1) were associated with the resistance for gemcitabine. PAK4 down-regulation through siRNA induced the up-regulation of hENT1, which is well-known as predictive marker for gemcitabine activity. In resistance cell lines (Capan-2, PANC-1, SNU-410), down-regulation of PAK4 through siRNArestored the drug-sensitivity for gemcitabine. In conclusion, PAK4 can be a potential predictive marker and therapeutic target in gemcitabine chemotherapy for pancreatic cancer. Citation Format: Sung Ung Moon, Jin Won Kim, Ji Hea Sung, Mi Hyun Kang, Hyun Chang, Jeong Ok Lee, Yu Jung Kim, Keun Wook Lee, Jee Hyun Kim, Soo Mee Bang, Jong Seok Lee. P21-activated kinase 4 (PAK4) as a predictive marker for gemcitabine in pancreatic cancer cell line. [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 912. doi:10.1158/1538-7445.AM2014-912
40. Correction of Dyslipidemia in Murine and Feline Models of Lipoprotein Lipase Deficiency by Intramuscular Administration of AAV1-LPLS447X
Authors: Colin J. D. Ross, Jaap Twisk, Jan Albert Kuivenhoven, Guoqing Liu, Fudan Miao, Karen van den Oever, Maarten Beetz, Dennis Verbart, Andrew Bakker, Paul P. A. Oranje, Wim T. Hermens, Paul Dijkhuizen, John J. P. Kastelein, Janneke J. M. Meulenberg, Michael R. Hayden
Journal: Molecular Therapy (2004)

Lipoprotein lipase (LPL) deficiency is characterized by excessive plasma triglyceride levels (TG), resulting in visibly milky plasma and severe clinical symptoms including life-threatening pancreatitis. There is no treatment for this inherited metabolic disease. We therefore proposed to test LPL gene therapy, expressing the human LPL variant S447X in muscle. This naturally-occurring variant is associated with a beneficial lipid profile in man, and improved disease correction over wild type LPL following adenoviral transfer to LPL deficient (LPL−/−) mice. To realize long-term correction of hypertriglyceridemia, adeno-associated virus serotype 1 (AAV1) was used to instill stable expression of LPLS447X in muscle. IM administration of 8×1011–8×1012 gc/kg AAV1-LPLS447X in LPL−/− mice was sufficient to reduce plasma TG levels (by up to 98%, from 99 to 1.8 mmol/L). These beneficial effects were observed within 1 week post-transfer, and lasted for >1 year. Importantly, only a fraction of LPL activity ( 98% reduction of plasma TG within 1 week. After 3 weeks, antibodies against human LPL were detected in plasma, and TG levels returned to pre-treatment levels. In accordance, LPL expression was greatly reduced. In contrast to LPL−/− mice that have low residual levels of LPL activity and protein, LPL−/− cats have no detectable LPL protein mass. Therefore, administration of LPLS447X to LPL−/− cats likely provoked an immune response that abrogated treatment efficacy. CONCLUSION: AAV1-mediated delivery of LPLS447X to muscle provides immediate correction of hypertriglyceridemia in two different animal models of LPL deficiency.
Neoplastic Hepatocyte Growth Associated with Ccylin D1 Redistribution from the Cytoplasm to the Nucleus in Mouse Hepatocarcinogenesis
Authors: Masahiro Yamamoto, Susumu Tamakawa, Masumi Yoshie, Yuji Yaginuma, Katsuhiro Ogawa
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4908 

In chemically-induced mouse hepatocarcinogenesis, colonies of carcinogen-altered hepatocytes emerge in early stage, which later progress to adenomas and finally to hepatocellular carcinomas (HCC). Analyses of cell cycle proteins revealed that cyclin D1, cyclin E, p27, cdk2 and cdk4 are overexpressed in the neoplastic hepatocytes from early stage and that cyclin D1 is mainly localized in their cytoplasm. When the animals bearing the hepatic lesions were subjected to partial hepatectomy, cyclin D1 was shifted from the cytoplasm to the nucleus in association with proliferation of the neoplastic hepatocytes, but it returned to the cytoplasm in association with termination of proliferation. When the cells derived from mouse HCC were cultured in the medium containing growth factors (insulin plus EGF)/10% FBS, cyclin D1 was also localized in the nucleus in association with cell proliferation, while in the absence of growth factors/FBS it was localized in the cytoplasm without cell proliferation. To understand the intracellular signals necessary for the nuclear shift of cyclin D1, we treated the cells with various inhibitors to signal transduction. Inhibition of phosphatidyl-inositol-3-phosphate kinase (PI3K) by Ly294002 prevented both cyclin D1 nuclear shift and cell proliferation. Knockdown of phosphatase and tensin homolog (PTEN) by siRNA activated the PI3K pathway, but it induced neither cyclin D1 nuclear shift nor cell proliferation, suggesting that the PI3K activation is necessary but not sufficient for the cyclin D1 nuclear shift. Although MEK inhibition by PD098059 or mTOR inhibition by rapamycin less affected both on the cyclin D1 nuclear shift and cell proliferation, it decreased the cyclin D1 expression. Finally, because the proteins bound to cyclin D1 may determined the cyclin D1 localization, we analysed the cyclin D1 complex in the proliferating and quiescent states. Although p27, cdk4 and calmodulin were detected in the cyclin D1 immunoprecipitates from both the quiescent and proliferating cells, Hsc70 and SSeCKS were detected only in those from the quiescent cells, and p21 only in those from the proliferating cells. These observations indicate that 1) the nuclear/cytoplasmic cyclin D1 localization plays an important role in proliferation/quiescence of neoplastic hepatocytes, 2) the PI3K pathway may be mainly responsible to relocalization of cyclin D1 to the nucleus, while the MAPK pathway may be mainly responsible to the cyclin D1 abundance, and 3) the nuclear/cytoplasmic localization of cyclin D1 may be dependent on the proteins bound to cyclin D1.
Mutations in the tyrosine phosphatase CD45 gene in a child with severe combined immunodeficiency disease
Authors: Chun Kung, Jeanette T. Pingel, Markku Heikinheimo, Timo Klemola, Kari Varkila, Lina I. Yoo, Katri Vuopala, Minna Poyhonen, Matti Uhari, Martin Rogers, Samuel H. Speck, Talal Chatila, Matthew L. Thomas
Journal: Nature Medicine (2000)
The Biologic and Clinical Basis of Infectious Diseases.
Authors: Guy P. Youmans, Philip Y. Paterson, Herbert M. Sommers
Journal: Annals of Internal Medicine (1977)

Section I: Host-Microbe Interactions. Section II: Upper Respiratory Tract Infection and Sequelae. Section III: Lower Respiratory Tract Infection. Section IV: Genitourinary Infections. Section V: Gastrointestinal Tract Infections. Section VI: Central Nervous System Infections. Section VII: Infection in the Immunocompromised Host. Section VIII: Additional Infections. Section IX: Treatment and Prevention of Infectious Diseases.
The roles of loss of heterozygosity at 8p22 in the molecular classification of patients with hepatocellular carcinoma, with special reference to survival after surgical operation
Authors: Lun-Xiu Qin, Jin-Zhong Pang, Ning Ren, Qing-Hai Ye, Zhao-You Tang
Journal: Clinical Cancer Research (2006)

B54    Purpose: Our previous studies have demonstrated that chromosome 8p deletion, particularly 8p11-12 and 8p21-23, correlates with metastasis of human hepatocellular carcinoma (HCC). The purpose of this study was to determine whether allelic losses on these regions including 8p could be used in predicting the prognosis of patients with HCC. Experimental Design:  A total of 208 patients with TNM stage I or II of HCC who underwent curative liver resection from January 1999 to March 2000 were enrolled. Genomic DNA was extracted from microdissected HCC tissues. LOH was examined using 10 microsatellite markers located at the regions of chromosome 8p mentioned above, and its association with 5-year overall survival (OS) and disease-free survival (DFS) of patients was analyzed. Results:  The mean heterozygosity of these loci was 69.8%. The LOH frequencies assessed from informative cases at the loci tested were also high, with a range from 32.6% (D8S1721) to 48.8% (D8S261), and the three most frequently altered loci were D8S261(8p22). In univariate analyses, LOH on D8S29857 (8p22) (39.6%) was associated with a worse 5-year OS ( P =0.037) and DFS ( P  P =0.008) and DFS ( P =0.038). In a multivariate model, D8S298 LOH was one of the independent predictors for decreased DFS (P=0.019) and decreased OS (P=0.014). Conclusion:  LOH at D8S298 is independently associated with a worse survival in stage I and II patients with curative resection for HCC.v:textbox>v:textbox>