tbuckley/cabot-search huggingface dataset:
Image-guided targeted intraarterial delivery of chemotherapy drug loaded iron oxide nanoparticles to rabbit liver cancer model.
Authors: Hyun Sik Kim, Taoreed O Lawal, Veronica E Prieto, Jing Huang, Liya Wang, Hui Mao
Journal: Journal of Clinical Oncology (2012)

e14734 Background: To develop an enhanced drug delivery system to liver tumors using novel MRI traceable iron oxide nanoparticles (IONP) loaded with doxorubicin and to investigate biodistribution of deliverednanoparticle and by assessing intratumoral and normal liver tissue concentrations after targeted (IA) versus systemic (IV) administration. Methods: Paramagnetic IONP (core and hydrodynamic size of 10 nm and 23 nm, respectively) coated with amphiphilic polymers were non-covalently loaded with hydrophobic doxorubicin; whose presence was confirmed by optical absorption spectrum. VX2 liver tumors were induced in the left lobe of 12 rabbits, allowed to grow for 2 weeks to a size of 2 cm, and were subsequently divided into 2 treatment groups, each receiving 1 mg/kg body weight of doxorubicin via IONP. Group 1 received IA administration to the left hepatic artery under fluoroscopy, and Group 2 received IV administration via the marginal ear vein. Animals were sacrificed 24 hours after treatment. Tumor and liver sections were collected and iron concentrations of tumor and liver tissues were determined by the colorimetric method with iron binding 1,10-phenanthroline at 508 nm. Analysis of tissue iron concentrations in different groups was performed using a standard t-test, with p&lt;0.05 considered significant. Results: Intratumoral and peritumoral concentrations of IONP were significantly higher 24 hours after IA administration than IV (1.54 vs 1.03 mg Fe/g , p=0.019), given at the same dosage. Additionally, 24 hours after treatment, the group receiving IA therapy showed significantly higher nanoparticle concentrations in the left hepatic lobe in comparison to the IV group (1.63 vs 1.34 mg Fe/g, p=0.0226). Conclusions: Targeted IA delivery significantly enhances intratumoral and peritumoral uptake of IONP when compared to IV. Targeted intraarterial delivery of IONP carrying doxorubincin can serve as a powerful tool in serving as a vehicle to deliver chemotherapy drugs to liver tumors. To further evaluate the potential of this drug delivery method, future studies will correlate the biodistrubution of the IONP to drug concentrations and findings on histology, imaging, tumor response.
mTOR inhibition leads to increased sensitivity to methotrexate
Authors: Guray Saydam, Hilal Celikkaya, Peter Cole, Joseph R. Bertino, Emine A. Ercikan-Abali
Journal: Cancer Research (2005)

3303  The mammalian target of rapamycin (mTOR) is an important player in the regulation of cell proliferation, growth, differentiation and survival. mTOR regulates both the activity of the 40S ribosomal protein S6 kinase and the eukaryotic initiation factor 4E-binding protein 1 (4E-BP1). This pathway also regulates the translation of mRNAs (e.g. cyclin D1) that are important for the G1/S transition. Inhibition of mTOR pathway increases the rate of turnover of cyclin D1. The cyclin D/CDKs phosphorylate pRb and release the E2Fs which mediate the transcription of proteins required for DNA synthesis, such as dihydrofolate reductase (DHFR). In a variety of cancers, including leukemia and lymphomas the Cyclin D-Cdk4,6/INK4/Rb/E2F pathway is deregulated and contributes to tumor development and also drug resistance towards antifolates. For example, inactivation of p16 and p15 genes, one of the most common genetic events in acute leukemia, is associated with increased DHFR expression and plays an important role in the pathogenesis of acute leukemia. Moreover, the PI3K/Akt/PTEN, the upstream regulators of mTOR pathway are also deregulated in leukemia and lymphomas. Mutations and hemizygous deletions of PTEN have been shown in some primary acute leukemia and non-Hodgkin’s lymphomas, and many hematopoietic cell lines. Akt1 is also frequently translocated in leukemia and lymphoma. Expression of DHFR is regulated both at the transcriptional through the Rb pathway and at the translational levels. We therefore hypothesized that by inhibiting mTOR pathway DHFR levels would be downregulated due to accelerating cyclin D1 degradation or by reducing the levels of DHFR translation through attenuation of 4E-BP1 phosphorylation. To test our hypothesis, four leukemic cell lines were used; namely CEM-S, K562, SKI-DLCL and HL60. The sensitivity of these cell lines against MTX and rapamycin was measured using the XTT assay. Briefly, in each well of a 96-well plate 4000 cells were plated in 300μL of medium containing the desired concentration of drug, and after 5 days, the XTT assay was performed according to standard protocols. After determining the IC50 values of each drug, the sensitivity of these leukemic cells against MTX in the presence of rapamycin at a concentration that corresponds to IC20 of these cell lines with rapamycin alone were determined. The addition of rapamycin sensitized the cells with lymphoblastic origin to MTX approximately 100-fold. We are currently measuring the levels of the proteins involved in the Rb pathway and the mTOR pathway to determine the mechanism of the observed sensitization. Our studies are also underway with combination studies using RAD001, which is a rapamycin analog that is being developed as an antiproliferative agent and other antifolates targeting DHFR and thymidylate synthase.
Pocket Handheld Ultrasound As a Novel Point-of-Care Imaging Modality to Diagnose Bleeding in Hemophilic Joints
Authors: Jenny Y Zhou, Katherine C. Rappazzo, Lena Volland, Bruno Steiner, Rebecca Kruse-Jarres, Doris V. Quon, Eric Y. Chang, Annette von Drygalski
Journal: Blood (2016)
Bone Marrow Mesenchymal Stromal Cells Transfer Their Mitochondria to Acute Myeloid Leukaemia Blasts to Support Their Proliferation and Survival
Authors: Christopher Marlein, Lyubov Zaitseva, Rachel E Piddock, Stephen Robinson, Dylan R Edwards, Manar S Shafat, Kristian M Bowles, Stuart A Rushworth
Journal: Blood (2016)
Expression and Therapeutic Potential of SOX9 in Chordoma
Authors: Hua Chen, Cassandra C. Garbutt, Dimitrios Spentzos, Edwin Choy, Francis J. Hornicek, Zhenfeng Duan
Journal: Clinical Cancer Research (2017)

Purpose: Conventional chemotherapeutic agents are ineffective in the treatment of chordoma. We investigated the functional roles and therapeutic relevance of the sex-determining region Y (SRY)-box 9 (SOX9) in chordoma.Experimental Design: SOX9 expression was examined by immunohistochemistry (IHC) using 50 chordoma tissue samples. SOX9 expression in chordoma cell lines was examined by Western blot and immunofluorescent assays. We used synthetic human SOX9 siRNA to inhibit the expression of SOX9. Cell proliferation ability and cytotoxicity of inhibiting SOX9 were assessed by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) and clonogenic assays. The effect of SOX9 knockdown on chordoma cell motility was evaluated by a wound-healing assay and a Transwell invasion chamber assay. Knockdown of SOX9 induced apoptosis, cell-cycle arrest, as well as decreased expression of cancer stem cell markers were determined by Western blot and flow cytometric assays. The effect of the combination of SOX9 siRNA and the chemotherapeutic drug doxorubicin/cisplatin on chordoma cells was assessed by an MTT assay.Results: Tissue microarray and IHC analysis showed that SOX9 is broadly expressed in chordomas and that higher expression levels of SOX9 correlated with a poor prognosis. RNA interference (RNAi)-mediated knockdown of SOX9 inhibited chordoma cell growth, decreased cell motility, and induced apoptosis as well as cell-cycle arrest. Moreover, the combination of SOX9 inhibition and chemotherapeutic drugs had an enhanced anti-cancer effect on chordoma cells.Conclusions: Our results demonstrate that SOX9 plays a crucial role in chordoma. Targeting SOX9 provides a new rationale for treatment of chordoma. Clin Cancer Res; 23(17); 5176-86. ©2017 AACR.
Abstract 323: Arginine Methylation Regulates Epicardial Cell Plasticity
Authors: Jian Xu, Juan Oses-Prieto, Alma Burlingame, Rik Derynck
Journal: Circulation Research (2013)

Kinase activation and substrate phosphorylation commonly form the backbone of signaling cascades. TGFbeta family ligands induce activation of their signaling effectors, the Smads, through C-terminal phosphorylation by transmembrane receptor kinases following type I and type II receptor complex formation. Here we show that arginine methylation, which regulates gene expression, yet also modifies some signaling mediators, initiates TGFbeta-induced Smad signaling. TGFbeta-induced receptor complex formation promotes presentation of the methyltransferase PRMT1 to the inhibitory Smad7, resulting in Smad7 methylation at a specific arginine as revealed by mass spectrometry analysis and confirmed with a mutagenesis approach. Antibodies specific for asymmetric di-methylated arginine further confirmed Smad7 methylation and Smad7 recruitment to the cell membrane upon TGFbeta stimulation. TGFbeta-induced and PRMT1-mediated Smad7 methylation leads to Smad7 dissociation from TGFbeta type I receptors, allowing activation of effector Smads through phosphorylation. This PRMT1-mediated Smad7 methylation is required in TGFbeta-regulated epicardial plasticity, as apparent by the role of PRMT1 in TGFbeta-induced epithelial-to-mesenchymal trans-differentiation and transcriptional reprogramming in mouse epicardial cells.
Dietary Fats and Cardiovascular Disease: A Presidential Advisory From the American Heart Association
Authors: Frank M. Sacks, Alice H. Lichtenstein, Jason H.Y. Wu, Lawrence J. Appel, Mark A. Creager, Penny M. Kris-Etherton, Michael Miller, Eric B. Rimm, Lawrence L. Rudel, Jennifer G. Robinson, Neil J. Stone, Linda V. Van Horn
Journal: Circulation (2017)

Cardiovascular disease (CVD) is the leading global cause of death, accounting for 17.3 million deaths per year. Preventive treatment that reduces CVD by even a small percentage can substantially reduce, nationally and globally, the number of people who develop CVD and the costs of caring for them. This American Heart Association presidential advisory on dietary fats and CVD reviews and discusses the scientific evidence, including the most recent studies, on the effects of dietary saturated fat intake and its replacement by other types of fats and carbohydrates on CVD. In summary, randomized controlled trials that lowered intake of dietary saturated fat and replaced it with polyunsaturated vegetable oil reduced CVD by ≈30%, similar to the reduction achieved by statin treatment. Prospective observational studies in many populations showed that lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat is associated with lower rates of CVD and of other major causes of death and all-cause mortality. In contrast, replacement of saturated fat with mostly refined carbohydrates and sugars is not associated with lower rates of CVD and did not reduce CVD in clinical trials. Replacement of saturated with unsaturated fats lowers low-density lipoprotein cholesterol, a cause of atherosclerosis, linking biological evidence with incidence of CVD in populations and in clinical trials. Taking into consideration the totality of the scientific evidence, satisfying rigorous criteria for causality, we conclude strongly that lowering intake of saturated fat and replacing it with unsaturated fats, especially polyunsaturated fats, will lower the incidence of CVD. This recommended shift from saturated to unsaturated fats should occur simultaneously in an overall healthful dietary pattern such as DASH (Dietary Approaches to Stop Hypertension) or the Mediterranean diet as emphasized by the 2013 American Heart Association/American College of Cardiology lifestyle guidelines and the 2015 to 2020 Dietary Guidelines for Americans.
Use of Adjuvant Chemotherapy After Surgery in Patients With Colon Cancer
Authors: Lucio N. Gordan, Michael Diaz
Journal: JAMA Surgery (2017)

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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast 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 Surgery journal
Outcomes of PCI in Relation to Procedural Characteristics and Operator Volumes in the United States
Authors: Alexander C. Fanaroff, Pearl Zakroysky, David Dai, Daniel Wojdyla, Matthew W. Sherwood, Matthew T. Roe, Tracy Y. Wang, Eric D. Peterson, Hitinder S. Gurm, Mauricio G. Cohen, John C. Messenger, Sunil V. Rao
Journal: Journal of the American College of Cardiology (2017)
Inhibition of the phosphatidylinositol 3’-kinase (PI3K) signaling pathway selectively enhances paclitaxel-induced apoptosis by modulating AKT and BAD phosphorylation in ovarian cancer cells
Authors: Xiao-Feng Le, Amy Lammayot, Yiling Lu, Gordon B. Mills, Robert C. Bast
Journal: Cancer Research (2004)

3851   Phosphatidylinositol 3’-kinase (PI3K) plays a key role in a wide array of biological and pathophysiological processes, particularly in carcinogenesis. About 40% of ovarian cancers possess aberrant PI3K or AKT function. Thus, ovarian cancers may be appropriate targets for therapy with inhibitors of the PI3K pathway. We have previously demonstrated that the PI3K inhibitor LY294002 significantly decreased OVCAR-3 cell growth  in vitro  and  in vivo . Paclitaxel is an increasingly important agent for treating ovarian cancer. Alteration of the PI3K pathway could modulate sensitivity to several drugs including paclitaxel. Inhibition of PI3K enhanced paclitaxel-induced apoptosis in OVCAR-3 cells  in vitro  and  in vivo . We have now treated a greater number of ovarian cancer cell lines with a PI3K inhibitor and paclitaxel and found substantial heterogeneity in sensitivity to this combination. In some ovarian cancer cell lines, such as MDA-2774 and ES-2, the LY294002 strikingly potentiated paclitaxel-induced apoptosis. Conversely, the PI3K inhibitor did not increase paclitaxel-induced apoptosis in some ovarian cancer cell lines such as SKOv3 and OVCA433. In ovarian cancer cell lines that are sensitive to the combination, treatment with LY294002 and paclitaxel synergistically suppressed the serine and threonine phosphorylation of AKT and BAD. Phosphorylation of AKT and BAD is known to regulate the function of AKT and BAD in apoptosis. On the other hand, the phosphorylation of AKT and BAD was not synergistically inhibited by LY294002 and paclitaxel combination in ovarian cancer cell lines that are insensitive to the combination. These observations are consistent with the hypothesis that inhibition of PI3K signaling pathway selectively enhances paclitaxel-induced apoptosis by modulating AKT and BAD phosphorylation in ovarian cancer cell lines. (This work was supported by a grant 80094241 from Goodwin Foundation and in part by agent CA-39930 from the National Institute of Health).
A multicenter study of patients decisional control preferences in patients with advanced cancer.
Authors: Sriram Yennu, Luis Fernando Rodrigues, Omar M. Shamieh, Columbe Tricou, Marilène Filbet, Kyaw Naing, Akhileswaran Ramaswamy, Pedro Emilio Perez-Cruz, Mary Joycylyn S. Bautista, Sofia Bunge, Mary Ann Muckaden, Vikash Sewram, Sarah Fakrooden, Antonio Noguera Tejedor, Shobha S Rao, Janet L. Williams, Hilda Cantu, David Hui, Suresh K. Reddy, Eduardo Bruera
Journal: Journal of Clinical Oncology (2016)

6578 Background: The frequency of passive decisional control (pt prefers physician to make decisions) has been reported to be variable but generally larger among pts living in developing countries. This study aimed to determine the frequency of passive DCP among patients with advanced cancer (ACP) in different cancer centers across the world. To identify the association of passive DCP with their socio-demographic and clinical characteristics. Methods: 1492 ACP referred to palliative care in 11 countries underwent assessment of decisional control preferences using a validated tools including Control Preference Scale tool, Satisfaction with Decision Scale and understanding of illness questionnaire. Information regarding patient characterstics including age, gender, education, marital status, employment, Karnofsky Performance Scale, cancer stage and type, religion were also collected. Descriptive statistics and Logistic regression analysis were performed. Results: Median age was 58 years, karnofsky 70, and 55% were female. Shared, Active (pt prefers to make decision by his/her own) and Passive DCP were 33.1%, 43.3% and 22.4% respectively (n=1492). 89.6% were satisfied by the way the actual decisions were made. 727 (49.4%) felt that their cancer was curable. Shared(range 14 %-53%), Active(range 15%-73%) and Passive DCP (range 6-44%) was significantly different across countries (P<.001) (Table 1). Multivariate analysis shows that the passive DCP was significantly associated in employment status {retired pts, OR .42; P<.009)} and religion {muslims, OR 2.2; P=0.01}. Conclusions: There are significant culture specific differences in DCP. Therefore, individualized assessment of DCP is important for quality cancer care and patient satisfaction outcomes. Passive decisional control preferences. N (%) OR P value USA 31(15.5) 1.0 - Argentina 6 (6.0) .35 .023 Brazil 25 (10.5) .64 .12 Chile 20 (20.0) 1.36 .33 France 75 (37.5) 3.27 <.001 India 43 (44.3) 4.34 <.001 Singapore 14 (13.1) .82 .56 South Africa 9 (11.8) .73 .44 Spain 6 (11.1) .68 .42 Philippines 22 (22.0) 1.54 .17 Jordan 77 (38.5) 3.41 <.001
Fired researcher who shot medical school dean is convicted of attempted murder
Authors: Owen Dyer
Journal: BMJ (2017)

A disgraced former researcher who shot the dean of Mount Sinai’s Icahn School of Medicine in New York has been convicted of attempted murder, criminal use of a firearm, and first degree assault. He faces up to 25 years in prison.

Hengjun Chao, 50, claimed in court that he shot psychiatrist Dennis Charney, 66, in an attempt to draw publicity to corruption he had discovered at the medical school.

Chao shot Charney as the dean emerged from a delicatessen holding a coffee, early in the morning on his way to work.1 The shooting was captured on security video, as was Chao’s staking out the delicatessen for four days previously.

Seeing Charney emerge, …
The association of Tabacco smoke with subclinical atherosclerosis and atherosclerosis progression is stronger in women than in men
Authors: E. Tremoli, F. Veglia, M. Amato, A. Ravani, D. Sansaro, C. Tedesco, A. Discacciati, B. Frigerio, S. Castelnuovo, D. Baldassarre
Journal: Circulation (2010)
Turkish National Severe Congenital Neutropenia Registry
Authors: Deniz Yilmaz Karapinar, Zeynep Karakas, Turkan Patıroglu, Ayse Metin, Umran Caliskan, Tiraje Celkan, Baris Yilmaz, Tuba H. Karapinar, Serap Karaman, Burcu Akıncı, Himmet Haluk Akar, Huseyin Tokgoz, Gul Nihal Ozdemir, Ayça Aslan Kıykım, Yurdanur Kılınç, Yesim Oymak, Lale Olcay, Ozcan Bor, Zuhal Keskin YILDIRIM, Muge Gokce, Erol Erduran, Dilber Talia Ileri, Yusuf Ziya Aral, Ali Bay, Berna Atabay, Zühre Kaya, Hüseyin Onay, Ferda Özkınay, Bilge Ozsait Selçuk, Ugur Ozbek, Gulsun Tezcan Karasu, Sebnem Yilmaz Bengoa, Akif Yesilipek
Journal: Blood (2016)
Long-term outcomes after disease activity-guided dose reduction of TNF inhibition in rheumatoid arthritis: 3-year data of the DRESS study - a randomised controlled pragmatic non-inferiority strategy trial
Authors: Chantal AM Bouman, Noortje van Herwaarden, Frank HJ van den Hoogen, Jaap Fransen, Ronald F van Vollenhoven, Johannes WJ Bijlsma, Aatke van der Maas, Alfons A den Broeder
Journal: Annals of the Rheumatic Diseases (2017)

Tumour necrosis factor inhibitors (TNFi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR). We aimed to assess long-term outcomes of TNFi DR in RA by using 3-year data from the DRESS study (Dose REduction Strategy of Subcutaneous TNF inhibitors study).In the intervention phase (month 0-18) of the DRESS study (Dutch trial register, NTR 3216), patients were randomised to DR or usual care (UC). In the extension phase (month 18-36), treatment strategies in both groups converged to continuation of protocolised tight control and allowed dose optimisation. Intention-to-treat analyses were done on flare, disease activity (28 joint count-based disease activity score with C reactive protein (DAS28-CRP)), functioning (health assessment questionnaire-disability index (HAQ-DI)), quality of life (Euroqol 5 dimensions 5 levels questionnaire (EQ5D-5L)), medication use, radiographic progression (Sharp van der Heijde score (SvdH)) and AE.172/180 patients included in the DRESS study were included in the extension phase. Cumulative incidences of major flare were 10% and 12% (-2%, 95% CI -8 to 15) in DR and UC groups in the extension phase, and 17% and 14% (3%, 95% CI -9 to 13) from 0 to 36 months. Cumulative incidences of short-lived flares were 43% (33 to 52%)%) and 35% (23 to 49%)%) in DR and UC groups in the extension phase, and 83% (75 to 90%)%) and 44% (31 to 58%)%) from 0 to 36 months. Mean DAS28-CRP, HAQ-DI, EQ5D-5L and SvdH remained stable and not significantly different between groups. TNFi use remained low in the DR group and decreased in the UC group. Cumulative incidences of AE were not significantly different between groups.Safety and efficacy of disease activity guided TNFi DR in RA are maintained up to 3 years, with a large reduction in TNFi use, but no other benefits. Implementation of DR would vastly improve the cost-effective use of TNFi.
Identifying Novel Modifiers of Embryonic Globin Expression By Combining Chipseq, Rnaseq and eQTL Mapping in the Adult Nan Mouse Model
Authors: Danitza Nebor, Kevin R. Gillinder, Raymond F. Robledo, Joel H. Graber, Vivek Philip, Melissa Ilsley, James J. Bieker, Andrew Perkins, Luanne L. Peters
Journal: Blood (2016)
Hotspots of missense mutation identify neurodevelopmental disorder genes and functional domains
Authors: Madeleine R Geisheker, Gabriel Heymann, Tianyun Wang, Bradley P Coe, Tychele N Turner, Holly A F Stessman, Kendra Hoekzema, Malin Kvarnung, Marie Shaw, Kathryn Friend, Jan Liebelt, Christopher Barnett, Elizabeth M Thompson, Eric Haan, Hui Guo, Britt-Marie Anderlid, Ann Nordgren, Anna Lindstrand, Geert Vandeweyer, Antonino Alberti, Emanuela Avola, Mirella Vinci, Stefania Giusto, Tiziano Pramparo, Karen Pierce, Srinivasa Nalabolu, Jacob J Michaelson, Zdenek Sedlacek, Gijs W E Santen, Hilde Peeters, Hakon Hakonarson, Eric Courchesne, Corrado Romano, R Frank Kooy, Raphael A Bernier, Magnus Nordenskjöld, Jozef Gecz, Kun Xia, Larry S Zweifel, Evan E Eichler
Journal: Nature Neuroscience (2017)