tbuckley/cabot-search huggingface dataset:
Elevated p21-activated protein kinase 2 activity suppresses anoikis of breast cancer cells
Authors: Andrew Eaton, Jerry Marlin, Yu-Wen Chang, Rolf Jakobi
Journal: Cancer Research (2008)

1830  For metastasis to occur, cancer cells must acquire the ability to invade and survive in circulation. Normal epithelial cells die via anoikis (detachment-induced apoptosis) when detached from the epithelial layer because they loose contacts of integrin receptors with proteins in the extracellular matrix. Metastatic cancer cells escape from anoikis by constitutive activation of signaling pathways downstream of integrin receptors which enables them to survive and even grow in circulation. p21-activated protein kinases (PAKs) have been shown to act in signaling pathways downstream of integrin receptors and are frequently elevated in protein and/or activity levels in breast cancer. To examine if elevated PAK-2 activity enables breast cancer cells to escape anoikis, we have generated Hs578T breast cancer cells with a conditionally active PAK-2 construct. Expression and activation of this PAK-2 construct increases PAK-2 activity levels in Hs578T cells, which contain low levels of endogenous PAK-2 activity. The elevated PAK-2 activity results in enhanced resistance to anoikis and anchorage-independent survival and growth of Hs578T cells. Expression and activation of the conditionally active PAK-2 construct also changes pro- and anti-apoptotic signaling pathways. Phosphorylation of Bad and ERK increases indicating enhanced cell survival and growth signaling. Levels of active caspase 3 and cleavage of the caspase 3 substrate PARP decreases indicating reduced pro-apoptotic caspase cascade signaling. PAK-2 itself is a substrate of caspase 3 and caspase cleavage converts the anti-apoptotic PAK-2 into the pro-apoptotic PAK-2p34 fragment. Interestingly, expression and activation of the conditionally active PAK-2 construct also decreases caspase cleavage of PAK-2 indicating that elevated PAK-2 activity interferes with its own caspase cleavage. It is suggested that elevated PAK-2 activity results in enhanced resistance to anoikis of breast cancer cells by stimulation of anti-apoptotic signaling and suppression of pro-apoptotic signaling including its own processing to the pro-apoptotic PAK-2p34 fragment.
Effect of Linagliptin on Cognitive Performance in Patients With Type 2 Diabetes and Cardiorenal Comorbidities: The CARMELINA Randomized Trial
Authors: Geert Jan Biessels, Chloë Verhagen, Jolien Janssen, Esther van den Berg, Bernard Zinman, Julio Rosenstock, Jyothis T. George, Anna Passera, Sven Schnaidt, Odd Erik Johansen
Journal: Diabetes Care (2019)

OBJECTIVE Type 2 diabetes is associated with cognitive dysfunction and an increased dementia risk, particularly in individuals with concomitant cardiovascular and/or kidney disease. Incretin therapies may modulate this risk via glycemic and nonglycemic pathways. We explored if the dipeptidyl peptidase 4 inhibitor linagliptin could prevent cognitive decline in people with type 2 diabetes with cardiorenal disease. RESEARCH DESIGN AND METHODS The CArdiovascular and Renal Microvascular outcomE study with LINAgliptin (CARMELINA)-COG substudy was an integral part of CARMELINA (NCT01897532) that randomized participants with cardiorenal disease to linagliptin 5 mg or placebo once daily (1:1), in addition to standard of care. The primary cognitive outcome was the occurrence of accelerated cognitive decline at the end of treatment, defined as a regression-based index score ≤16th percentile on the Mini-Mental State Examination (MMSE) or a composite measure of attention and executive functioning and analyzed in participants with a baseline MMSE ≥24. Effects across subgroups by baseline factors, as well as absolute cognitive changes, were also assessed. RESULTS Of the 6,979 participants in CARMELINA, CARMELINA-COG included 1,545 (mean ± SD age, 68 ± 8 years; MMSE, 28.3 ± 1.7; estimated glomerular filtration rate, 52 ± 23 mL/min/1.73 m2; and HbA1c, 7.8 ± 0.9% [61.4 ± 10.1 mmol/mol]). Over a median treatment duration of 2.5 years, accelerated cognitive decline occurred in 28.4% (linagliptin) vs. 29.3% (placebo) (odds ratio 0.96 [95% CI 0.77, 1.19]). Consistent effects were observed across subgroups by baseline characteristics. Absolute cognitive performance changes were also similar between treatment groups. CONCLUSIONS In a large international cardiovascular outcome trial in people with type 2 diabetes and cardiorenal disease, linagliptin did not modulate cognitive decline over 2.5 years.
Management of Infections in SCD Patients Treated with HU in the Framework of Escort HU
Authors: Frédéric Galactéros, Malika Benkerrou, Mariane De Montalembert, Jean-Antoine Ribeil, Corinne Pondarré, Jean Benoît Arlet, Uwe Kordes, Regine Grosse, Valentine Brousse, Lena Oevermann, Stephan Lobitz
Journal: Blood (2017)
Resistance to TRK inhibition mediated by convergent MAPK pathway activation
Authors: Emiliano Cocco, Alison M. Schram, Amanda Kulick, Sandra Misale, Helen H. Won, Rona Yaeger, Pedram Razavi, Ryan Ptashkin, Jaclyn F. Hechtman, Eneda Toska, James Cownie, Romel Somwar, Sophie Shifman, Marissa Mattar, S. Duygu Selçuklu, Aliaksandra Samoila, Sean Guzman, Brian B. Tuch, Kevin Ebata, Elisa de Stanchina, Rebecca J. Nagy, Richard B. Lanman, Brian Houck-Loomis, Juber A. Patel, Michael F. Berger, Marc Ladanyi, David M. Hyman, Alexander Drilon, Maurizio Scaltriti
Journal: Nature Medicine (2019)
Communication Strategies for Sharing Prognostic Information With Patients
Authors: Joanna Paladino, Joshua R. Lakin, Justin J. Sanders
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
PTU-077 Reduction of intravenous opiate use on a gastroenterology ward
Authors: P Fortun, J Huddy, A Flynn, K Mitchell, H Falvey
Journal: Gut (2017)

Introduction  The Medical Gastroenterology Ward in our District General Hospital was identified as a relatively high prescriber of intravenous (IV) and oral opiate analgesia, and intravenous and oral cyclizine, compared to other wards. This was in the context of a cohort of challenging patients with nonspecific abdominal pain and unexplained medical symptoms (UMS). A strategy to define the problem and manage opiate use for non-malignant pain was developed then evaluated.  Method  Intravenous (IV) and oral use of opiates on each of the Medical wards of our hospital was measured, in units of oral morphine equivalent (OME), as well as cyclizine. A multidisciplinary group was formed comprising a Consultant Anaesthetist/Pain Management Specialist, Liaison Psychiatry, Clinical Psychology, Pharmacy. The team based approach to restricting opiate use in frequent attenders, or UMS patients included education of medical and nursing staff around opiate awareness, an opiate policy with guidance for maximum 48 hour IV opiate use before non parenteral use, care management plans, and development of an early warning system from our information analyst in Pharmacy to identify patients on IV morphine for 48 hours to cue discussion between the Pain team and the treating Physician.  Results  The Medical Gastroenterology ward was an outlier in terms of prescription of high total doses of IV morphine and oral morphine or oral morphine equivalent (OME). Comparing 2015 and 2016, The Gastroenterology ward achieved a reduction in oral (or OME) and IV morphine use of 44% and 75% respectively. Over th esame time period, these values were unchanged for the other 5 Medical wards, excpet the MAU wherer oral and IV morphine prescription fell by 9% and 41% respectively. This may have included similar patients with nonspecific abdominal pain or UMS. Cyclizine prescription remained high no reduction in IV use. REduction in opiate use in Gastroenterology was not associated with any reduction in length of stay.  Conclusion  A team based comprehensive pain management stategy targeted at a Medical Gastroenterology ward coincided with a dramatic reduction in intravenous opiate use, whilst there was no corresponding trend on other Medical wards. We propose to expand the strategy to patients with non-specific abdominal pain and undiagnosed medical symptoms requiring opiate analgesia. We also plan to embed opiate management in a wider program of managing UMS, and opate use in Primary Care.  Disclosure of Interest  None Declared
Combination of Surgery With Extensive Intraoperative Peritoneal Lavage for Patients With Advanced Gastric Cancer
Authors: Bee-Choo Tai, Asim Shabbir, Jimmy So
Journal: JAMA Surgery (2019)

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
Personalized adaptive instruction design (PAID) for brain–computer interface using reinforcement learning and deep learning: simulated data study
Authors: A. Eliseyev, T. Aksenova
Journal: Brain-Computer Interfaces (2019)

Brain–computer interface (BCI) systems may require the user to perform a set of mental tasks, such as imagining different types of motion. The performance demonstrated on these tasks varies with time and between users. This study presents a new method for the automatically adaptive, user-specific generation of a sequence of tasks to increase the effectiveness of user training. For this purpose, we developed the Personalized Adaptive Instruction Design (PAID) algorithm, which uses reinforcement learning and deep learning. Using simulated data, we compared the training strategy developed here with uniform random and sequential selection strategies. The results demonstrate that the PAID strategy outperforms the others and is close to the theoretically optimal solution. Moreover, our algorithm offers the possibility of efficiently integrating psychological aspects of the training process into the generated strategy.
Characterization of two bi-functional anti-HER2/neu IgG3-cytokine fusion proteins with potential use as cancer therapeutics
Authors: Gustavo F. Helguera, Vivian R. Kyinn, Christine Lowe, Jay S. Dela Cruz, Ryan Trinh, Patrick P. Ng, Sherie L. Morrison, Manuel L. Penichet
Journal: Cancer Research (2004)

4669  A number of studies have now reported that combining different cytokines will have powerful synergistic effects resulting in an enhanced immune response against cancer. The synergistic effects of cytokines IL12/IL2 and IL12/GM-CSF in enhancing the immune response make these combinations attractive as potential therapeutic tools. Furthermore, targeting of cytokines to the tumor microenvironment through linkage to monoclonal antibodies can significantly improve the therapeutic indexes of the cytokines. We have previously demonstrated that anti-HER2/neu IgG3-(IL2), (IL12)-IgG3 and IgG3-(GM-CSF) fusion proteins exert significant anti-tumor activity against a murine tumor expressing human HER2/neu. To further explore the utility of antibody fusion proteins in the treatment of cancer, we have now produced two novel bi-functional anti-human HER2/neu IgG3-cytokine fusion proteins (bi-Ab-FPs) with scIL12 fused to the N-terminus of IgG3-(IL2) and of IgG3-(GM-CSF). Both constructs, expressed in murine myeloma cells, were properly assembled and secreted. ELISA experiments showed that the bi-Ab-FPs bind specifically to the soluble extracellular domain of human HER2/neu and flow cytometry demonstrated that both bi-Ab-FP can bind to human HER2/neu expressed on the surface of the murine colon carcinoma cell line CT26. Both bi-Ab-FPs retained the IL12 activity as demonstrated by dose-dependent enhancement of the proliferation of human PBMC cells pulsed with PHA. The IL12/IL2 bi-Ab-FP also showed dose dependent enhancement of the proliferation of the IL2 dependent cell line CTLL2. Finally, (IL12)-IgG3-(GM-CSF) was able to support proliferation of GM-CSF dependent FDC-P1 cells as measured by MTS colorimetric assay. All bioactivity assays were specific for the tested cytokines and were unaffected by the presence in the same molecule of the other cytokine. These studies demonstrate the feasibility of producing bi-functional anti-human HER2/neu IgG3-cytokine fusion proteins which should direct the functional activity of both cytokine components to their tumor target. It is expected that the combination of the two cytokines in the same molecule may result in potent synergistic anti-tumor response in patients bearing cancers from breast and ovary that shows marked over-expression of HER2/neu, a condition that is associated with poor prognosis. Further in vivo and in vitro studies are currently underway.
MicroRNAs expression in acute promyelocitic leukemia upon ATRA treatment
Authors: Tiziana M. Palumbo, Ramiro Garzon, Flavia Pichiorri, Amelia Cimmino, Rodolfo Iuliano, Stefano Volinia, Sylvia Wojcik, George Adrian Calin, Chang Gong Liu, Carlo Maria Croce
Journal: Cancer Research (2006)

3251  MicroRNAs are small non-protein coding RNAs of 19 to 25 nucleotides that regulates gene expression targeting messenger RNAs (mRNA) in a sequence specific manner inducing translational repression or mRNA degradation depending on the degree of complementarity between miRNAs and their targets . For the few microRNAs whose function is known, they play important roles in development, differentiation, metabolism, cell growth and death in animals and plants. Recently microRNAs have been described to be involved in the regulation of mice hematopoiesis and to be disregulated in chronic lymphocytic leukemias and other lymphoproliferative disorders of B origin. However little is known about miRNAs are regulated and their role in myelopoiesis. Acute Promyelocytic leukemia (APL) is a subtype of acute myelogenous leukemia, which results from the translocation of the promyelocytic gene (PML) gene in the chromosme 15 and the retinoic acid receptotr alpha gene ( RARa) in chromosome 17. . This traslocation creates a novel oncogenic fusion protein which induces maturation arrest at the promyelocytic stage of granulocytic diffrentiation Pharmacological dosis of all-trans-retinoic acid (ATRA) reverse the dominant negative effect of the oncogenic protein fusion PML-RARa and induce differentiation of APL cells in vitro and in vivo . Indeed this is one of the best studied cell models of differentiation. In the present study, we analyze the microRNAs expression in APL cell lines upon ATRA treatment using microRNAs microarrays. Among the up-regulated microRNAs upon ATRA treatment, three microRNAs are predicted to target the same gene, which is a recently discover hematopoietic transcription factor involved in myeloid differentiation. Furthermore we identified and validated several other microRNA targets, which are genes activated by ATRA and involved in retinoic acid signaling. Thus, ATRA simultaneously induced retinoic acid signaling genes and modulate their expression throught a microRNA based mechanism.
Experience of 34 Years of Multiple Myeloma in a Reference Center of a Developing Country
Authors: Maria Cynthia Fuentes Lacouture, Leonardo Camacho, Javier Segovia, David Suarez, Monica Duarte, Guillermo Quintero, Myriam Lucía Rodriguez, Oscar Rivero, Lina Abenoza, Andres Borda, Patricia Bernal, Oscar Torres, Carlos Saavedra, Sandra Quijano, Fernando Alvarado, Zoila Conrado, Gina Cuellar, Liliana Martin, Adriana Plata, Oscar Martinez, Jose De La Hoz, Martha Romero Prieto
Journal: Blood (2017)
CD133 expression before and after radiation in glioblastoma multiforme
Authors: Ron Ellsworth, James Welsh, Rachit Kumar, Kyle Fjerstad, Sylvan Green, Ray Nagle, Baldassarre Stea
Journal: Cancer Research (2008)

1010  BACKGROUND: Cancer stem cells have recently emerged as the population responsible for resistance to therapy which may lead to tumor recurrence. This subpopulation of stem cells often demonstrates CD133 positivity. It has been shown that the CD133+ brain tumor cells population increases with irradiation (XRT) in vitro. However, no data has been published regarding in vivo human correlates. We hypothesize that the population of CD133+ cells might be increased in tumors that have received radiation and have clinically recurred. We therefore looked at a patient population with glioblastoma multiforme (GBM) for whom we could find specimens at the time of initial diagnosis and at recurrence after radiation with the objective of correlating the CD133 expression levels with their survival.  METHODS: Tissue microarrays were constructed with matched specimens from ten patients with confirmed GBM who underwent resection for diagnosis and at the time of recurrence (post-XRT). Immunohistochemistry was performed using a CD133 antibody (Abcam). Scores were determined by rating the strength of staining on a scale of 0-3; this number was multiplied by the percentage of cells staining positively. Staining level was compared to overall patient survival.  RESULTS: Five of the ten patients demonstrated increased staining for CD133 at the time of recurrence. Their initial average score was zero, while at the time of recurrence the average score was 12. Four patients did not express CD133 either at initial presentation or at the time of recurrence. One patient actually showed a decrease in CD133 at recurrence (initial score 20, recurrent score 3). The average survival for the five patients with an increase in CD133 expression was 16 months (range 6-32). The average survival for patients that did not express CD133 was 40 months (range 14-66). In this small patient population of 10 patients, there appears to be a strong correlation between CD133 expression levels and survival (p=0.04 by log-rank test).  CONCLUSIONS: This data suggests that an inverse correlation exists between increasing CD133+ cells and patient survival supporting the hypothesis that recurrence in GBM is the result of the enrichment of the tumor with CD133+ radiation resistant stem cells (supported by in vitro studies).This finding also highlights potential new approaches in the treatment of GBM that might target the subpopulation of CD133+ cells. A larger study incorporating more patient specimens is necessary to confirm this preliminary data.
High levels of carcinogenic polycyclic aromatic hydrocarbons in mate drinks
Authors: Farin Kamangar, Michele Schantz, Christian Abnet, Renato Fagundes, Sanford Dawsey
Journal: Cancer Research (2008)

5571  Background: Drinking mate, an infusion of the herb ilex paraguayensis (yerba mate), has been associated with cancers of the esophagus, oropharynx, larynx, lung, kidney, and bladder. We conducted this study to determine whether drinking mate could lead to substantial exposure to polycyclic aromatic hydrocarbons (PAHs), including known carcinogens such as benzo[a]pyrene.  Methods: The concentrations of 21 individual PAHs were measured in dry leaves of eight commercial brands of yerba mate, and in infusions made with hot (80 oC) or cold (4 oC) water and two commonly used brands. Measurements were performed using gas chromatography/mass spectrometry, with deuterated PAHs as the surrogates. Infusions were made by adding water to the leaves, steeping for 5 min, removing and storing the resulting infusion, and then adding more water to the remaining leaves. This process was repeated 12 times for each infusion temperature. PAHs released into these infusions (ng/g of dry leaves) were measured in infusions 1, 3, 6, and 12 and were inferred for the other eight.  Results: The total concentrations of the 21 PAHs in different brands of yerba mate ranged from 536 ng to 2906 ng per g of dry leaves. Benzo[a]pyrene concentrations ranged from 8.03 ng/g to 53.3 ng/g of dry leaves. For the mate infusions prepared using hot water and Brand 1, 37% (1092 ng out of 2906 ng) of the total measured PAHs and 50% (25.1 ng out of 50 ng) of the benzo[a]pyrene content were released into the 12 infusions. For the mate infusions prepared using cold water and Brand 1, 34% (999 ng out of 2906 ng) of the total PAH content and 56% (28.1 ng out of 50 ng) of the benzo[a]pyrene content were released into the 12 infusions. Similar results were obtained for infusions made from Brand 2.  Conclusion: Very high concentrations of carcinogenic PAHs were found in yerba mate leaves, and substantial portions of these compounds were released into hot and cold mate infusions. Our results suggest that benzo[a]pyrene intake associated with drinking mate may be comparable to that associated with smoking cigarettes, and they support the hypothesis that the carcinogenicity of mate may be related to its PAH content.
A pathogenic role of plasmacytoid dendritic cells in autoimmunity and chronic viral infection
Authors: Franck J. Barrat, Lishan Su
Journal: The Journal of Experimental Medicine (2019)

Following the discovery of plasmacytoid dendritic cells (pDCs) and of their extraordinary ability to produce type I IFNs (IFN-I) in response to TLR7 and TLR9 stimulation, it is assumed that their main function is to participate in the antiviral response. There is increasing evidence suggesting that pDCs and/or IFN-I can also have a detrimental role in a number of inflammatory and autoimmune diseases, in the context of chronic viral infections and in cancers. Whether these cells should be targeted in patients and how much of their biology is connected to IFN-I production remains unclear and is discussed here.