tbuckley/cabot-search huggingface dataset:
PWE-057 Impaired neutrophil phagocytic capacity in patients with advanced cirrhosis is related to the development of ammonia-induced neutrophil swelling
Authors: N J Taylor, R Abeles, M Hussein, Y Ma, J Wendon, D L Shawcross
Journal: Gut (2010)

<h3>Introduction</h3> Neutrophil phagocytic dysfunction is associated with increased risk of infection and mortality in patients with cirrhosis. Increased bacterial translocation from the gut generates a proinflammatory response in patients with cirrhosis and the resulting cytokine milieu leads to neutrophil priming and conformational changes in binding ligands which alters phagocytic capacity. A recent study has also shown that ammonia exposure induces neutrophil swelling and impairs phagocytosis. (1) This longitudinal study aimed to characterise the relationship between neutrophil function and volume, plasma cytokine profile and ammonia in a cohort of patients with advanced liver cirrhosis undergoing assessment for liver transplantation (LT), and 72 h following LT, compared to healthy controls (HC) (n=8). <h3>Methods</h3> Neutrophils were isolated from 26 patients with end-stage cirrhosis at baseline, and 72 h following LT (n=7/26) during the 18-month follow-up period. Phagocytosis was analysed by flow cytometry using FITC-labelled <i>E coli</i> and anti-CD16-PE IgG1 as a neutrophil stain. Neutrophil volume was measured by comparing the forward scatter of 10 000 gated neutrophils in their resting state using flow cytometry. Clinical data, blood biochemistry, arterial ammonia and microbial cultures were collected. Cytokine analysis for TNF-α, IL-1β, IL-6, IL-8, IL-10 and IL-17 were performed using ELISA. <h3>Results</h3> Neutrophil phagocytosis was significantly impaired in patients with advanced cirrhosis (p=0.007) and was associated with an 11.2% increase in neutrophil volume. In those who underwent uncomplicated LT, neutrophil volume and phagocytic capacity normalised within 72 h. Phagocytic impairment correlated with increasing plasma concentrations of the proinflammatory cytokines TNF-α (p=0.01), IL-6 (p=0.008) and IL-17 (p=0.03) and the anti-inflammatory cytokine IL-10 (p=0.08) but not with IL-1β or IL-8. Severe phagocytic impairment also predicted those who went on to develop sepsis and multi-organ dysfunction. Elevated arterial ammonia concentrations directly correlated with worsening neutrophil phagocytic dysfunction (r<sup>2</sup>=0.01, p=0.02). <h3>Conclusion</h3> These data demonstrate that impaired phagocytic capacity in patients with advanced cirrhosis is related to the development of ammonia-induced neutrophil swelling and is associated with poor outcomes in those who do not undergo LT.
Lymphoma and Pregnancy
Authors: Agustin Avilés, Marìa-Jesus Nambo, Natividad Neri
Journal: JAMA Oncology (2016)

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 Oncology 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 Oncology journal
Chemotherapy-Refractory Diffuse Large B-Cell Lymphomas (DLBCL) Are Effectively Killed by Ofatumumab-Induced Complement-Mediated Cytoxicity.
Authors: Saskia A.G.M. Cillessen, Wendy J.M. Mackus, Kitty C.M. Castricum, Wim Vos, Pim C. Kortman, Jan G.J. van de Winkel, Paul W.H.I. Parren, Chris J.L.M. Meijer, Joost J. Oudejans
Journal: Blood (2007)
In Acute Promyelocytic Leukemia (APL) Low BAALC Gene Expression Identifies a Group of Patients with Favorable Outcome in Overall Survival and Relapse Free Survival,
Authors: Florian Nolte, Anna Hecht, Daniel Nowak, Verena Nowak, Benjamin Hanfstein, Andreas Faldum, Thomas Buchner, Karsten Spiekermann, Cristina Sauerland, Wolf-Karsten Hofmann, Eva Lengfelder
Journal: Blood (2011)
Abstract 3940: Inactivation of the PARD3 gene is a recurrent event in lung squamous cell carcinomas and affects STAT3 activity and tumor invasiveness
Authors: Ester Bonastre, Sara Verdura, Ilse Zondervan, Federica Facchinetti, Sylvie Lantuejoul, Maria Dolores Chiara, Juan Pablo Rodrigo, Julian Carretero, David Sidransky, Alberto Villanueva, Enric Condom, Agustin Vidal, Luca Roz, Elisabeth Brambilla, Suvi Savola, Montse Sanchez-Cespedes
Journal: Cancer Research (2015)

Abstract Correct apicobasal polarization and intercellular adhesions are essential for the appropriate development of normal epithelia. Here, we investigated the contribution of the partitioning defective 3 gene, PARD3, to the carcinogenesis of lung squamous cell carcinomas (LSCCs). Tumor-specific PARD3 alterations were found in eight per cent of the tumors, placing PARD3 among the most common tumor suppressor genes in LSCC. Some PAR3 mutant proteins prevented the formation of contacts between neighboring cells, i.e. had reduced ability to form tight junctions and actin-based protrusions. This affected subsequent downstream signaling, i.e. binding to aPKC and activation of RAC1. Further, we discovered that PAR3 wild type triggered the expression of cell adhesion and polarity-related transcripts and the activation of STAT3, by cell confluence. Finally, restitution of PAR3 in vivo significantly reduced the formation of metastasis. In conclusion, PARD3 is recurrently inactivated in LSCC and its deficiency contributes to the tumor aggressiveness. Citation Format: Ester Bonastre, Sara Verdura, Ilse Zondervan, Federica Facchinetti, Sylvie Lantuejoul, Maria Dolores Chiara, Juan Pablo Rodrigo, Julian Carretero, David Sidransky, Alberto Villanueva, Enric Condom, Agustin Vidal, Luca Roz, Elisabeth Brambilla, Suvi Savola, Montse Sanchez-Cespedes. Inactivation of the PARD3 gene is a recurrent event in lung squamous cell carcinomas and affects STAT3 activity and tumor invasiveness. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3940. doi:10.1158/1538-7445.AM2015-3940
Abstract 840: Occupational exposure to trichloroethylene and LINE-1 methylation
Authors: Wei Hu, Luoping Zhang, Christopher Kim, Xiaojiang Tang, Sungkyoon Kim4, Bryan Bassig, Wei-Jie Seow, Min Shen, Chuangyi Qiu, Yechen Ge, Boris Reiss, Mark Purdue, Lee Moore, Laiyu Li, Fei Yue, Hanlin Huang, Martyn T. Smith, Roel Vermeulen, Nathaniel Rothman, Qing Lan
Journal: Cancer Research (2015)

Abstract Trichloroethylene (TCE) is a volatile chlorinated organic compound that is commonly used in industrial settings as a degreaser. Epidemiologic studies suggest that TCE exposure is associated with an increased risk of kidney cancer and may also be associated with non-Hodgkin lymphoma. However, the mechanisms for these associations are still not clear. To evaluate the relationship between occupational exposure to trichloroethylene (TCE) and LINE-1 methylation, a measure of global methylation, we conducted a cross-sectional molecular epidemiology study of 79 workers exposed to TCE and 81 comparable unexposed controls in Guangdong, China. Personal air exposure measurements and urine samples were collected prior to phlebotomy. The urine TCE metabolite, trichloroacetic acid (TCA), was measured by liquid chromatography electrospray ionization tandem mass spectrometry in urine samples and LINE-1 methylation was assessed by pyrosequencing DNA isolated from peripheral blood. LINE-1 methylation levels [median (range) in percent] were 78.40 (75.80-81.20) in controls, 77.80 (76.10-81.00) in lower exposed, and 77.50 (74.20-80.20) in higher exposed workers based on median urine TCA level (p trend = 0.012). These results suggest that TCE may be associated with a decrease in global methylation measured by the LINE-1 assay. Gene-specific methylation is currently being conducted to follow up these findings. Citation Format: Wei Hu, Luoping Zhang, Christopher Kim, Xiaojiang Tang, Sungkyoon Kim4, Bryan Bassig, Wei-Jie Seow, Min Shen, Chuangyi Qiu, Yechen Ge, Boris Reiss, Mark Purdue, Lee Moore, Laiyu Li, Fei Yue, Hanlin Huang, Martyn T. Smith, Roel Vermeulen, Nathaniel Rothman, Qing Lan. Occupational exposure to trichloroethylene and LINE-1 methylation. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 840. doi:10.1158/1538-7445.AM2015-840
An Unusual Presentation of Congenital Dyserythropoietic Anemia Type II (CDAII) Associated with Severe Anemia in a Patient with a Novel Mutation of the SEC23B Gene
Authors: Melanie A Villanueva, Carol J Saunders, David Zwick, Laurie Smith, Darrell Dinwiddie, Emily Farrow, Neil Miller, Stephen Kingsmore, Keith J. August
Journal: Blood (2012)
Abstract 2144: Kinetic mechanism of the lysine methyltransferase SMYD3 using MAP3K2 protein substrate
Authors: Thomas V. Riera, Tim J. Wigle, Jodi Gureasko, P. Ann Boriack-Sjodin, Robert A. Copeland
Journal: Cancer Research (2015)

Abstract Dysregulation of DNA and histone methylation has been shown to play fundamental roles in carcinogenesis. Recently however, protein methylation in the cytoplasm has been linked to oncogenic Ras signaling. Mazur and colleagues demonstrated that SMYD3 (SET and MYND domain containing protein 3), a primarily cytoplasmic protein methyltransferase, can methylate MAP3K2 using S-adenosyl-L-methionine (SAM) as a cofactor (Mazur et al. 2014. Nature 510(7504):283-7). Methylation by SMYD3 preserves the active, phosphorylated state of MAP3K2 sustaining activation of the Ras/Raf/MEK/ERK/ signaling module and potentiating formation of Ras-driven cancers. Here, we characterized the kinetic mechanism of SMYD3 using MAP3K2 protein as a substrate. SMYD3 activity was measured with a radiometric assay using 3H-SAM. Initial velocity, product and dead-end inhibitor studies indicate that SMYD3 uses a random kinetic mechanism where both SAM and MAP3K2 can bind apo-SMYD3. This was supported by substrate and ligand binding assays using SPR. Together, these studies elucidate the kinetic mechanism of SMYD3 with MAP3K2 and provide a context for inhibitor development. Citation Format: Thomas V. Riera, Tim J. Wigle, Jodi Gureasko, P. Ann Boriack-Sjodin, Robert A. Copeland. Kinetic mechanism of the lysine methyltransferase SMYD3 using MAP3K2 protein substrate. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2144. doi:10.1158/1538-7445.AM2015-2144
Sustained Virologic Response Rate of Hepatitis E Virus Infection Treated With Ribavirin may be Lower in Asian Kidney Transplant Recipients
Authors: Sarah En Xian Low, Edhel Santiago Tripon, How Cheng Low, Poh Seng Tan, Yin Mei Lee, Kieron Lim, Yock Young Dan, Seng Gee Lim, Guan-Huei Lee
Journal: Clinical Gastroenterology and Hepatology (2016)
Identification of Escape Mechanisms Involved in the Absence of Viral Control Despite Activation of Both Innate (natural killer and gammadelta T cells) and Virus-Specific T Cells in Children with CMV or EBV Disease Following Cord Blood Transplantation.
Authors: Laure Farnault, Gerard Michel, Herve Chambost, Didier Blaise, Sabine Furst, Felix Montero, Emmanuel Gautherot, Julie gertner-Dardenne, Ivan Hirsch, Francoise gondois-Rey, Daniel Olive
Journal: Blood (2009)
Allogeneic Stem Cell Transplantation for Elderly Patients with Intermediate-Risk Cytogenetic Acute Myeloid Leukemia and Internal Tandem Duplication of FLT3 (FLT3-ITD); A Study from the Acute Leukemia Working Party (ALWP) of the European Society of Blood and Marrow Transplantation (EBMT)
Authors: Xavier Poiré, Myriam Labopin, Jakob R Passweg, Charles Craddock, Didier Blaise, Jan Cornelissen, Liisa Volin, Nigel H. Russell, Gerard Socie, Mauricette Michallet, Yosr Hicheri, Patrice Chevallier, Gernot Stuhler, Norbert Ifrah, Mohamad Mohty, Jordi Esteve, Arnon Nagler
Journal: Blood (2015)
Abstract 2716: Epstein-Barr virus-encoded BARF1 downregulates SMAD4 and increases miR-146a in gastric carcinoma cells
Authors: Dong Ha Kim, Chan Jin Yoon, Jin Kyung Rho, Jaap M. Middeldorp, Jun Hee Woo, Mee Soo Chang
Journal: Cancer Research (2015)

Abstract Recently, molecular analytic data from ‘The Cancer Genome Atlas’ (TCGA) (http://www.cbioportal.org) has re-confirmed that Epstein-Barr virus (EBV)-infected gastric carcinoma is a specialized subset of gastric carcinomas. However, viral oncogene has not yet been established in gastric carcinomas. Several reports have suggested that EBV-encoded BARF1 may be a putative viral oncogene in gastric carcinoma. The aim of this study was to investigate alterations of cellular microRNA and cellular protein by BARF1 in gastric carcinoma cells. We cloned BARF1 from naturally EBV-infected gastric carcinoma cell line, and transfected BARF1 into EBV-negative gastric carcinoma cells, thus produced a stable cell line of BARF1-transfected gastric carcinoma cells. BARF1-transfected gastric carcinoma cells revealed significantly increased cellular proliferation than its original cells. The MicroRNA array (Agilent release 16.0) data and Taqman RT-PCR results showed that cellular miR-146a was highly expressed in BARF1-transfected gastric carcinoma cells, comparing to that in original cells. In BARF1-transfected gastric carcinoma cells, transfection with BARF1-siRNA offset the increment effect of miR-146. Using bioinformatics analyses for miR-146a target (RNA hybrid 2.2 and TargetScan 5.2 sites), we found that miR-146a target seed sequence existed in the 3′ UTR of SMAD4 mRNA. The Western blot assay demonstrated that SMAD4 was remarkably reduced by BARF1 transfection. When immunohistochemistry for SMAD4 was performed on 343 cases of surgically resected, human gastric carcinoma tissues, 32 (9%) EBV-infected gastric carcinoma group disclosed more frequent loss of SMAD4 than EBV-negative group. In conclusion, EBV-encoded BARF1 could promote proliferation of gastric carcinoma cells, thereby contributing to EBV-induced cancer progression, in which SMAD4 downregulation, probably through miR-146a increase, may be entailed. Citation Format: Dong Ha Kim, Chan Jin Yoon, Jin, Kyung Rho, Jaap M. Middeldorp, Jun Hee Woo, Mee Soo Chang. Epstein-Barr virus-encoded BARF1 downregulates SMAD4 and increases miR-146a in gastric carcinoma cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2716. doi:10.1158/1538-7445.AM2015-2716
Abstract 525: PHD3-mediated prolyl hydroxylation of non-muscle actin impairs polymerization and cell motility
Authors: Weibo Luo, Gregg L. Semenza
Journal: Cancer Research (2015)

Abstract Actin filaments play an essential role in cell movement and many post-translational modifications regulate actin filament assembly. Here we report that prolyl hydroxylase 3 (PHD3) interacts with non-muscle actin in human cells and catalyzes hydroxylation of actin at proline residues 307 and 322. Blocking PHD3 catalytic activity, by either a pharmacological inhibitor or short hairpin RNA knockdown of PHD3 expression, decreases actin prolyl hydroxylation. Knockdown of PHD3 significantly increases filamentous F-actin assembly, which is reversed by PHD3 overexpression. PHD3 knockdown significantly increases cell velocity and migration distance. Inhibition of PHD3 prolyl hydroxylase activity by dimethyloxalylglycine also increases actin polymerization and cell migration. These data reveal a novel role for PHD3 as a negative regulator of cell motility through post-translational modification of non-muscle actins. Citation Format: Weibo Luo, Gregg L. Semenza. PHD3-mediated prolyl hydroxylation of non-muscle actin impairs polymerization and cell motility. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 525. doi:10.1158/1538-7445.AM2015-525
FluCam—a New, 4-Weekly Combination of Fludarabine and Alemtuzumab for Patients with Relapsed Chronic Lymphocytic Leukemia.
Authors: Thomas Elter, P. Bochmann, H. Schulz, M. Reiser, S. Trelle, P. Staib, T. Schinkothe, M. Hallek, Andreas Engert
Journal: Blood (2004)
649. Targeting Innate Host Immunity Through PI3K Delta for Enhancement of Systemic Delivery of Oncolytic Vaccinia Virus
Authors: Mark Ferguson, James Tysome, Ellie Burns, Maria Whitehead, Ezra Aksoy, Andrew Clear, Ghassan Alusi, Crispin Hiley, Bart Vanhaesebroeck, Nicholas R. Lemoine, Yaohe Wang
Journal: Molecular Therapy (2015)

Oncolytic vaccinia virus (VV) has shown promise for the delivery of gene therapy and has the potential to be delivered systemically to treat metastatic cancer. VV is known to induce a strong host immune response, which requires immunocompetent models for evaluation. We investigated the systemic delivery of oncolytic vaccinia virus to murine tumours in immunocompetent mice using tumour-targeted oncolytic vaccinia virus and found that VV was unable to efficiently infect tumours due to clearance, mostly by splenic macrophages. Depletion of macrophages using clodronate liposomes (CL) facilitated the systemic delivery of vaccinia virus to subcutaneous, established murine tumours. However CL non-selectively deplete macrophages and potentially diminish any beneficial macrocytic activity in the tumour microenvironment unrelated to viral clearance. Consequently, a more appropriate agent is needed. Macrophages recognise and ingest pathogenic microorganisms through phagocytosis, a process for which several lines of evidence have highlighted an important role for phosphatidylinositol 3-kinases. Thus, PI3K inhibitors could potentially enhance systemic delivery of VV. Eight mammalian isoforms of PI3K exist, but the specific isoforms involved in macrophage phagocytosis of VV have not been elucidated. In this study, we, for the first time, demonstrated that PI3K delta is a major player affecting monocytes to clear vaccine virus. IC87114 (p110 delta inhibitor) is effective at reducing uptake of VV by macrophages. Subsequently, it was confirmed that IC87114 affects attachment of the virus to macrophages but plays no role in internalisation. Furthermore IC87114 is neither directly toxic to a panel of cancer cells nor oncolytically additive nor synergetic when combined with VV in vitro. Biodistribution studies have established that IC87114 combined with VV results in statistically more virus detected in tumours compared to the VV alone treated groups with similar limited off target effects. Finally three different efficacy studies have demonstrated statistically significant superior tumour response in IC87114 group. In conclusion, p110 delta blockade is an effective strategy for enhancing systemic deliver of VV in a pre-clinical model and could be a useful adjuvant in VV clinical trials
Abstract 734: Synergistic antitumor effect of vemurafenib and metformin in thyroid cancer
Authors: Elyse K. Hanly, Neha Y. Tuli, Robert B. Bednarczyk, Augustine L. Moscatello, Zbigniew Darzynkiewicz, Jan Geliebter, Raj K. Tiwari
Journal: Cancer Research (2015)

Abstract Advanced thyroid cancer patients such as those with radioiodine-refractory and metastatic differentiated thyroid cancer or anaplastic thyroid cancer lack effective treatment options. Targeted BRAF kinase inhibitors such as vemurafenib have shown promising results in clinical trials and off-label use for patients with BRAFV600E-positive tumors. While targeting BRAFV600E offers particular effectiveness and selectivity in inhibiting cancer cells in the short term, resistance does develop. Prior results in our laboratory confirmed that vemurafenib halts DNA synthesis and induces apoptosis in our mutated thyroid cancer cells. In addition, resistant BCPAP (papillary thyroid cancer) cells were developed in our laboratory by exposing cells to increasing concentrations of vemurafenib. Resistant cells were characterized by hyperactive mitogen-activated protein kinase (MAPK) signaling and resistance to mammalian target of rapamycin (mTOR) inhibition. These additional targets mediating resistance provide an opportunity to devise novel synergistic combination therapies. Since antitumor effects of the widely used antidiabetic agent metformin were observed in thyroid cancer cells and the drug is thought to suppress mTOR, we investigated metformin adjuvant therapy in combination with vemurafenib. Various cell lines including Nthy-ori 3-1 (normal immortalized thyroid cells), BCPAP (papillary thyroid cancer), vemurafenib-resistant BCPAP, and 8505c (anaplastic thyroid cancer) were analyzed in terms of cellular viability, apoptosis and expression of cell signaling molecules after exposure to both drugs. We found that the combination of vemurafenib and metformin caused significantly decreased viability in vemurafenib-resistant BCPAP cells. Furthermore, synergistic apoptosis was observed in BCPAP papillary thyroid cancer cells and 8505c anaplastic thyroid cancer cells in response to the combination treatment. These effects appeared to be mediated by inhibition of both mTOR and MAPK signaling. Results support further investigation into the use of metformin in combination with targeted kinase inhibitors to treat advanced thyroid cancer patients. Citation Format: Elyse K. Hanly, Neha Y. Tuli, Robert B. Bednarczyk, Augustine L. Moscatello, Zbigniew Darzynkiewicz, Jan Geliebter, Raj K. Tiwari. Synergistic antitumor effect of vemurafenib and metformin in thyroid cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 734. doi:10.1158/1538-7445.AM2015-734