tbuckley/cabot-search huggingface dataset:
Connexin43 induced breast tumor cell re-differentiation in three-dimensional cultures
Authors: Elizabeth McLachlan, Qing S. Shao, Dale W. Laird
Journal: Cancer Research (2004)

1460  Normal human mammary epithelium expresses gap junction proteins Cx43 and Cx26, however, gap junctions are frequently down-regulated in breast tumors. We have previously shown that the human breast tumor cell line MDA-MB-231 expresses low levels of endogenous Cx43 and exhibits sparse gap junctional intercellular communication (GJIC). Over-expression of Cx43 by retroviral infection in these cells resulted in little rescue of GJIC with the majority of the connexin being prematurely routed to lysosomes (Qin et al., 2003, JBC 278, 30005). Although there was no effect of connexin over-expression on 2D cell growth, when these cells were implanted into nude mice a dramatic suppression of tumor growth was observed with no apparent increase in gap junctions (Qin et al., 2002, JBC, 277, 29132). Furthermore, when these cells were cultured in soft-agar, colony formation was significantly inhibited in Cx43 or Cx26 over-expressing cells. In more recent studies, when grown in 3D matrigel, control MDA-MB-231 cells formed undifferentiated stellate structures, indicative of a malignancy. In contrast, cells over-expressing Cx43 exhibited growth control and formed more spherical structures indicative of cell re-differentiation. We hypothesize that the effect of Cx43 over-expression on cell growth in 2D versus 3D is due to extracellular matrix signaling. Immunolocalization studies consistently revealed that most of Cx43 did not traffic to the membrane to form junctional complexes signifying that the mechanism for 3D growth control may be GJIC-independent or required little increase in GJIC. To examine the possible signaling pathways regulated by connexin expression in 3D cultures, we extracted RNA from 3D cultures of control and Cx43 over-expressing cells and subjected these preparations to bias gene arrays against human extracellular matrix and adhesion molecules. Currently we are identifying and verifying the genes regulated by Cx43 expression that trigger signal transduction pathway(s) important in mammary epithelial cell differentiation in 3D. Supported by a Canadian Breast Cancer Research Alliance (DWL) and a NSERC (EM).
Clonal Kinetics and Single Cell Transcriptional Profiling of Adoptively Transferred CD19 CAR-T Cells
Authors: Alyssa Sheih, Laila-Aicha Hanafi, Valentin Voillet, Hannah A. DeBerg, Reed M. Hawkins, Masanao Yajima, Vivian Gersuk, Peter S. Linsley, Raphael Gottardo, Cameron J. Turtle
Journal: Blood (2018)
AB0450 Impact of therapeutic patient education on safety skills and infectious events of patients treated by biological dmards in rheumatology: a bi-centric study
Authors: L. Frantzen, M. Ardizzone, L. Sparsa, D. Oréfice, N. Afif, L. Arnaud, J.-E. Gottenberg, J. Sibilia, C. Sordet
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients treated with biologic DMARDs have to be aware of the specific adverse events and have to be able to manage their treatments in case of infectious disease. Therapeutic Patient Education aims to enable patient to acquire these safety skills. <h3>Objectives</h3> To assess the impact of Therapeutic Patient Education on safety skills and management of infectious events in patients treated with biologic DMARDs in rheumatology. <h3>Methods</h3> Bi-centric analytical study comparing safety skills and infectious events between two cohorts of patients (TPE and TPE-naive). Safety skills were assessed by an auto-assessment called "Biosecure", rated on a scale from 0 to 100. This assessment explores several dimensions of treatment management and was validated for assessment of safety skills in patients treated with biologic DMARDs in rheumatology in a preliminary study. Infectious events and their management were self-reported by patients. A cluster analysis aimed to separate patients into working group based on their shortcomings (on the basis of their answers to the Biosecure Assessment). <h3>Results</h3> 414 patients answered the assessment. The median Biosecure Score was 70.98/100 (Q1Q3: 60.97–84.63) 47% attended Therapeutic Patient Education. The median Biosecure Score was significantly higher in the TPE group than in the TPE-naive group (74.88 versus 67.20/100; p&lt;0.05). Regarding the observance to treatment, activity scores, vaccination rates onf incidence of infectious events, there were no significant difference between the groups TPE and TPE-naive. Nevertheless, there were more treatment interruption for infectious events in the TPE group, suggesting that TPE could lead to better management of treatment during infectious events. Cluster analysis based on Biosecure assessment separated patients into 3 level groups but failed to identify specific patient profiles. <h3>Conclusions</h3> Therapeutic Patient Education could provide better safety skills and better treatment management in patients treated with biologic DMARDs in rheumatology. Prospective studies may confirm the impact of TPE on treatment management during infectious events. Further studies may assess the impact of TPE on incidence of serious infectious events. <h3>References</h3> [1] Orefice D, Beauvais C, Gossec L, Flipon E, Fautrel B, Marguerie L, et al. Cross-sectional study of self-care safety skills in 677 patients on biodrugs for inflammatory joint disease. Jt Bone Spine Rev Rhum. déc 2014;81(6):502. [2] Rat A-C, Fautrel B, Flipon E, Gossec L, Marguerie L, Nataf H, et al. Factors associated with knowledge and safety skills of arthritis patients receiving biologics: A survey of 677 patients. Joint Bone Spine. <h3>Disclosure of Interest</h3> None declared
Truncated proteins from frameshift mutation-derived mRNA of MARCKS are expressed in the colorectal carcinomas
Authors: kwon tae you, Hyun Ju Kang, Kwi Hye Koh, Kyoung Mi Kim, Yoon Ki Kim, Sung Mi Park, Sung Key Jang, Hoguen Kim
Journal: Cancer Research (2007)

5331  Frameshift and nonsense mutations are common in tumors, and mRNAs from these mutated genes have premature termination codons (PTCs). PTC-containing mRNAs are normally degraded by the nonsense-mediated mRNA decay (NMD), thus avoiding the potentially deleterious effects associated with the production of truncated proteins. However, PTCs located within 50 nucleotides of the last exon-exon junction are not recognized by NMD (NMD-irrelevant), and some PTC-containing mRNAs can escape from the NMD (NMD-escape). In order to clarify the protein expression status of affected genes with frameshift mutations and the role of NMD in these mutated genes, we selected MSI-H cancers as a model system because these cancers have accumulated genes with frameshift mutations, and the mRNAs expected from these mutated genes contain PTCs. We investigated protein expression from NMD-irrelevant and NMD-escape PTC-containing mRNAs by Western blotting and transfection assays. We demonstrated that transfection of NMD-irrelevant PTC-containing genomic DNA of MARCKS generates truncated protein. In contrast, NMD-escape PTC-containing versions of hMSH3,TGFBR2 generate similar levels of mRNA to wild type, but do not generate detectable levels of protein. Transfection of NMD-escape mutant TGFBR2 genomic DNA failed to generate expression of truncated proteins, while transfection of wild type TGFBR2 genomic DNA or mutant PTC-containing TGFBR2 cDNA generated expression of wild type protein and truncated protein, respectively. We also confirmed the translational repression is responsible for the failure to detect truncated protein from the NMD-escape mutant TGFBR2 genomic DNA by polysome assay. Our findings suggests 1) NMD-irrelevant mRNAs of MARCKS generate truncated proteins in tumors, 2) NMD-escape TGFBR2 mRNAs are translationally repressed by novel mechanism of gene expression regulation for PTC-containing mRNAs.
Abstract 19466: Testosterone Levels and Risk for Cardiovascular Events - A Report From the ORIGIN (Outcome Reduction With an Initial Glargine Intervention) Trial
Authors: Anne Wang, Stefan Arver, Kurt Boman, Viveca Gyberg, Sibylle Hess, Lars Rydén, Linda G Mellbin, Hertzel Gerstein
Journal: Circulation (2017)

Introduction: Low testosterone levels have been associated with increased risk for cardiovascular diseases and glucose perturbations in population-based studies. Information on the prognostic abili...
Venoarterial Extracorporeal Membrane Oxygenation for Cardiopulmonary Support
Authors: Peter Moritz Becher, Benedikt Schrage, Christoph R. Sinning, Bastian Schmack, Nina Fluschnik, Michael Schwarzl, Christoph Waldeyer, Diana Lindner, Moritz Seiffert, Johannes T. Neumann, Alexander M. Bernhardt, Uwe Zeymer, Holger Thiele, Hermann Reichenspurner, Stefan Blankenberg, Raphael Twerenbold, Dirk Westermann
Journal: Circulation (2018)
Хронічний панкреатит: про загальні положення щодо лікування
Authors: T.N. Hristich, D.O. Hontsariuk
Journal: GASTROENTEROLOGY (2018)

В огляді літератури обговорюються питання лікування абдомінального больового синдрому, синдрому зовнішньосекреторної недостатності підшлункової залози, супутніх хронічному панкреатиту дисфункції сфінктера Одді, жовчного міхура, жовчовивідних шляхів, дисбіозу, дискінезії кишечника згідно з положеннями останніх європейських рекомендацій та міжнародних консенсусів.
Abstract 17586: HSP27 Mediated Atheroprotection Requires GM-CSF Induction: Potential Role in Reverse Cholesterol Transport? <i>(Best of Basic Science Abstract)</i>
Authors: Vivek Krishna Pulakazhi Venu, Ayinuer Adijiang, Chunhua Shi, Yong-Xiang Chen, Edward R O’Brien
Journal: Circulation (2015)

Introduction: Previously, we demonstrated that Heat Shock Protein 27 (HSP27) reduces experimental atherogenesis and patients with elevated serum HSP27 levels are relatively protected against future CV events. We previously reported that extracellular HSP27 activates the NF-kB pathway and increases the expression of GM-CSF. While the potential atheroprotective role of GM-CSF remains controversial, clinical reports highlight its effect on reducing serum cholesterol levels. We now hypothesize that GM-CSF plays an important role in HSP27-mediated atheroprotection, potentially by up-regulating reverse cholesterol transport (RCT). Methods / Results: 1. NF-KB signaling in vitro: Treatment of macrophages with recombinant HSP27 (rHSP27) activated NF-kB 15-fold via TLR-4 (NF-kB reporter gene assay; controls: truncated rHSP27 peptide and TLR-4 deficient cells; p&lt;0.05). While rHSP27 substantially induced GM-CSF expression and secretion (300- and 400-fold respectively; p&lt;0.05) both processes were blocked by NF-kB inhibitors. 2. In vivo role of GM-CSF induction in HSP27-mediated atheroprotection: Aortic atherogenesis in apoE null treated with rHSP27 was reduced by an expected 40%, while ApoE null / GM-CSF null did not respond to rHSP27 treatment. Moreover, apoE null / GM-CSF null macrophages expressed ~33% lower levels of the reverse cholesterol transporters, ABC-A1 and ABC-G1. 3. rHSP27 &amp; Reverse Cholesterol Transport: THP-1 macrophages pre-treated with oxLDL and incubated with rHSP27 for 24h showed enhanced mRNA and protein expression of ABCA1 and ABCG1 (p&lt;0.01). In a RCT assay, THP-1 macrophages labeled with NBD-cholesterol and treated with rHSP27 for 24h before being incubated with apoA1 or HDL showed increased cholesterol efflux compared to controls (p&lt;0.0001 for both). Conclusion: HSP27 up regulates expression of GM-CSF that appears to play an important role in RCT-mediated atheroprotection.
Phase II Trial of a Peptide Vaccine, Ocv-501 in Elderly Patients with Acute Myeloid Leukemia
Authors: Masaki Yamaguchi, Naoki Takezako, Toru Kiguchi, Shuichi Miyawaki, Yuji Heike, Kaori Mitsuki, Takahiro Yoshida, Ei Leen Liew, Tomoki Naoe
Journal: Blood (2018)
Association of Fatality Risk With Value-Based Drug Pricing of Epinephrine Autoinjectors for Children With Peanut Allergy
Authors: Marcus Shaker, Matthew Greenhawt
Journal: JAMA Network Open (2018)

<h3>Importance</h3> The high cost of self-injectable epinephrine autoinjectors may represent a barrier to community anaphylaxis management. Value-based pricing can provide a benchmark for rational epinephrine autoinjector costs. <h3>Objective</h3> To define value-based pricing of community epinephrine autoinjectors. <h3>Design, Setting, and Participants</h3> In an economic evaluation study using a cost-effectiveness birth cohort model over an extended 80-year time horizon, Markov simulations of children with peanut allergy evaluated cost ceilings for value-based epinephrine prices in peanut allergy. Simulation inputs included all-cause age-adjusted mortality (2013 US life tables), 2013 published food allergy fatality rates, 2017 rates of autoinjector device carriage, and 2016 published market costs of self-injectable epinephrine. All costs were expressed in 2018 US dollars and discounted at 3% per annum. <h3>Exposures</h3> Cohorts of children with peanut allergy prescribed epinephrine autoinjectors were compared with those not receiving personal epinephrine prescriptions. Children without epinephrine autoinjectors assumed 10-fold to 100-fold fatality risk increases. Costs were evaluated from a societal perspective. <h3>Main Outcomes and Measures</h3> Fatality risk, quality-adjusted life-years, and incremental cost-effectiveness ratio. <h3>Results</h3> A total of 100 000 simulated infants with peanut allergy entered each strategy, with two-thirds of the group receiving annual personal epinephrine prescriptions and using those devices appropriately when indicated. Over the time horizon, the cost of anaphylaxis preparedness and treatment in those with personal epinephrine devices was $25 478 (95% CI, $25 399-$25 557) compared with $654 (95% CI, $645-$663) for those without personal epinephrine, resulting in an average food allergy fatality of 0.00056 (95% CI, 0.000414-0.000706) per patient prescribed self-injectable epinephrine and 0.00148 (95% CI, 0.001242-0.001718) in those not prescribed self-injectable epinephrine. The value-based price (incremental cost-effectiveness ratio, $100 000 per quality-adjusted life-year) for personal epinephrine based on 10-fold fatality risk difference was $24. At a market cost of $715 per twin pack, the autoinjector incremental cost-effectiveness ratio was $2 742 697 per quality-adjusted life-year. If a hypothetical fatality risk protection from personal epinephrine was modeled at 100-fold, the value-based price ceiling for a personal autoinjector was $264. <h3>Conclusions and Relevance</h3> In a simulation of children with peanut allergy, a value-based epinephrine cost has a ceiling of $24 for a personal autoinjector, even at an exaggerated fatality risk.
Two Cases of 188Re Microspheres for Inoperable Hepatocellular Carcinoma
Authors: Jaya Shukla, Naveen Kalra, Rajender Kumar, Priya Bhusari, Anupriya Chhabra, Madan Parmar, Rakhee Vatsa, Harmandeep Singh, Ajay Duseja, B. R. Mittal
Journal: Clinical Nuclear Medicine (2018)

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies. Often, patients present with inoperable and advanced disease. Selective internal radionuclide therapy offers prolonged survival and improved quality of life by delivering high radiation dose to the tumor with minimal complications. We report 2 inoperable cases of HCC treated with therapeutic dose of indigenously developed Re microspheres delivered to the hepatic lesions by transarterial catheterization. Follow-up CT revealed necrosis within the lesion, suggesting response to selective internal radionuclide therapy. Re microspheres may be a potential treatment option for inoperable HCC with or without portal vein thrombosis.
Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis
Authors: Changyu Zhu, KyeongJin Kim, Xiaobo Wang, Alberto Bartolome, Marcela Salomao, Paola Dongiovanni, Marica Meroni, Mark J. Graham, Katherine P. Yates, Anna Mae Diehl, Robert F. Schwabe, Ira Tabas, Luca Valenti, Joel E. Lavine, Utpal B. Pajvani
Journal: Science Translational Medicine (2018)

Aberrant hepatocyte Notch activation is required for development of NASH-associated fibrosis, and Notch inhibition ameliorates obesity-induced liver disease.
Diaphragmatic myotrauma: a mediator of prolonged ventilation and poor patient outcomes in acute respiratory failure
Authors: Ewan C Goligher, Laurent J Brochard, W Darlene Reid, Eddy Fan, Olli Saarela, Arthur S Slutsky, Brian P Kavanagh, Gordon D Rubenfeld, Niall D Ferguson
Journal: The Lancet Respiratory Medicine (2018)
In vitro and in vivo therapeutic effects of anti-NCA90 (CEACAM6) and anti-CEA (CEACAM5) antibody fab fragments
Authors: Rosalyn D. Blumenthal, Rosanna Michel, Louis Osorio, Hans J. Hansen, Ivan D. Horak, David M. Goldenberg
Journal: Cancer Research (2005)

691  Objective: CEA (CEACAM5) and NCA-90 (CEACAM6) are overexpressed in many types of cancer. We evaluated the anti-proliferation, anti-migration, anti-adhesion, and anti-invasion effects in vitro and the therapeutic effects in vivo of several antibodies targeting CEACAM6 and/or CEAMCAM5. Methods: In vitro studies were done on a panel of human pancreatic, breast and colonic cancer cell lines. Three antibodies (Abs) targeting different epitopes of NCA-90 and CEA were evaluated: MN-3 (N-domain), MN-15 (A1B1 domain), and MN-14 (A3B3 domain). Six in vitroassays were performed: growth inhibition by MTT, 3D spheroid assay, wound-healing migration assay, invasion through a membrane coated with extracellular matrix (ECM) proteins, adhesion to ECM proteins, and adhesion to endothelial cells (ECs). In vivo therapy studies with Abs alone ± a chemotherapeutic agent were done with the GW-39 human colonic intrapulmonary metastatic model. Results: None of the Abs inhibited growth of the parental MCA38 cell line (CEA-/NCA-90-). Growth in monolayer culture of MCA38cea cells (CEA+/NCA-90-), LS174T, Moser, and BT-20 cells (CEA+/ NCA90+) were inhibited by 8.0-33.3%, depending on the cell line and Ab used. Growth in 3D spheroid culture was strongly inhibited by MN-3>MN-15. MN-3 also induced a >50% decrease in cell migration. MN-15 was most effective Ab at inhibiting invasion, reducing cell penetration by 50-60%. MN-15 also caused a reduction in binding to fibronectin in 3/5 cell lines without affecting binding to laminin or vitronectin. All three Abs were able to inhibit adhesion of tumor cells to ECs by 15-96%, depending on the Ab and cell line. In vivo studies showed that pretreatment of GW-39 cells with MN-3 or MN-15 Fab increased host survival (P
GSK3β-mediated tau hyperphosphorylation triggers diabetic retinal neurodegeneration by disrupting synaptic and mitochondrial functions
Authors: Huazhang Zhu, Weizhen Zhang, Yingying Zhao, Xingsheng Shu, Wencong Wang, Dandan Wang, Yangfan Yang, Zhijun He, Xiaomei Wang, Ying Ying
Journal: Molecular Neurodegeneration (2018)

Although diabetic retinopathy (DR) has long been considered as a microvascular disorder, mounting evidence suggests that diabetic retinal neurodegeneration, in particular synaptic loss and dysfunction of retinal ganglion cells (RGCs) may precede retinal microvascular changes. Key molecules involved in this process remain poorly defined. The microtubule-associated protein tau is a critical mediator of neurotoxicity in Alzheimer's disease (AD) and other neurodegenerative diseases. However, the effect of tau, if any, in the context of diabetes-induced retinal neurodegeneration has yet to be ascertained. Here, we investigate the changes and putative roles of endogeneous tau in diabetic retinal neurodegeneration. To this aim, we combine clinically used electrophysiological techniques, i.e. pattern electroretinogram and visual evoked potential, and molecular analyses in a well characterized high-fat diet (HFD)-induced mouse diabetes model in vivo and primary retinal ganglion cells (RGCs) in vitro. We demonstrate for the first time that tau hyperphosphorylation via GSK3β activation causes vision deficits and synapse loss of RGCs in HFD-induced DR, which precedes retinal microvasculopathy and RGCs apoptosis. Moreover, intravitreal administration of an siRNA targeting to tau or a specific inhibitor of GSK3β reverses synapse loss and restores visual function of RGCs by attenuating tau hyperphosphorylation within a certain time frame of DR. The cellular mechanisms by which hyperphosphorylated tau induces synapse loss of RGCs upon glucolipotoxicity include i) destabilizing microtubule tracks and impairing microtubule-dependent synaptic targeting of cargoes such as mRNA and mitochondria; ii) disrupting synaptic energy production through mitochondria in a GSK3β-dependent manner. Our study proposes mild retinal tauopathy as a new pathophysiological model for DR and tau as a novel therapeutic target to counter diabetic RGCs neurodegeneration occurring before retinal vasculature abnormalities.
The High-Profile Patient—Ensuring Good Care for the Entire Hospital
Authors: Michael Nurok, Bruce Gewertz
Journal: JAMA Surgery (2018)

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The impact of continuing ALK inhibitors beyond initial disease progression on clinical outcome in patients with advanced ALK-positive non-small cell lung cancer: Results of a multicenter retrospective analysis
Authors: S. Sakata, S. Saeki, Y. Sakata, K. Kawamura, K. Ichikado, M. Inaba, S. Ushijima, K. Imamura, K. Iyonaga, T. Kumabe, R. Fujita, K. Kashiwabara, S. Fujii, T. Komatsu, O. Sakamoto, H. Okabayashi, K. Saruwatari, Y. Tomita, T. Sakagami
Journal: Annals of Oncology (2018)
Abstract 18598: Defibrillation Guided by Real-Time Ventricular Fibrillation Amplitude-Spectral Area Analysis Outperforms Guidelines-Driven Defibrillation During CPR in Swine
Authors: Raúl J Gazmuri, Christopher L Kaufman, Salvatore Aiello, Jeejabai Radhakrishnan, Alvin Baetiong, Steven A Miller
Journal: Circulation (2017)

Introduction: The amplitude spectral area (AMSA) of the ventricular fibrillation (VF) waveform serves to estimate the probability that an electrical shock could terminate VF and prompt return of sp...
Abstract 16375: Biomarkers Associated With Dense Calcium Increase in Coronary Plaque Under Statin Therapy
Authors: Tenjin Nishikura, Kohei Wakabayashi, Tsuyoshi Nozue, Shingo Yamamoto, Shinichi Tohyama, Kazuki Fukui, Shigeo Umezawa, Yuko Onishi, Tomoyuki Kunishima, Akira Sato, Toshihiro Nozato, Shogo Miyake, Hiroshi Suzuki, Yoshihiro Morino, Takao Yamauchi, Toshiya Muramatsu, Kiyoshi Hibi, Mitsuyasu Terashma, Kaoru Tanno, Ichiro Michishita
Journal: Circulation (2017)

Introduction: There is still residual risk in coronary artery disease (CAD) patients under statin therapy. Accumulation of coronary calcification is associated with cardiovascular events. The facto...
Polio eradication: next steps and future challenges
Authors: Maria Zambon, Javier Martin
Journal: Eurosurveillance (2018)

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