tbuckley/cabot-search huggingface dataset:
Abstract 1245: Peroxiredoxin induction in breast cancer
Authors: Valerie Buurma, Brendan Freeman, Akosua Adzenyah, Gregory Pettit, Felicitas Heinen, Jillian Muhlbauer, Shelley A. Phelan
Journal: Cancer Research (2015)

Abstract Cancer cells possess elevated levels of reactive oxygen species (ROS) that can enhance genomic instability and alter redox signaling. Aberrant antioxidant expression has also been recognized in many cancers, suggesting an adaptive response to the cancerous state. Breast cancers express significantly elevated levels of Peroxiredoxins (Prdxs), a family of thiol-specific antioxidant proteins involved in regulating cell growth and proliferation in many cell types. We previously reported overexpression of many Prdx proteins in the MCF-7 breast cancer line, as well as their importance in doxorubicin-resistance in this line. In the present study, we analyzed Prdx levels in several human breast tumor samples, and further investigated possible mechanisms of Prdx regulation in MCF-7 cells. Comparison of breast tumor and adjacent normal breast tissue from almost 20 patients showed that most patients exhibited elevated levels of several Prdx proteins in the tumor tissue. To begin to understand possible regulators of Prdxs in breast cancer, we focused on transcriptional regulators known to be aberrantly expressed in breast cancer, and also implicated in antioxidant regulation. Sequence analysis revealed potential binding sites for NF-κB, Nrf2, and AP-1 in several peroxiredoxin promoters. We found high levels of NF-κB in MCF-7 cells, as compared to normal breast epithelial cells. We further showed that a chemo-resistant MCF-7 culture generated from 14 days of doxorubicin treatment exhibited markedly decreased NF-κB expression. We then used both siRNA and chemical inhibition of NF-κB to examine the effect on Prdx regulation in these cells and found gene-specific effects. Similar studies are currently underway for Nrf2 and AP-1. This investigation will help to elucidate the role of peroxiredoxins in breast cancer cell survival, and the mechanism by which these cells alter Prdx levels to avoid death and achieve chemoresistance. Citation Format: Valerie Buurma, Brendan Freeman, Akosua Adzenyah, Gregory Pettit, Felicitas Heinen, Jillian Muhlbauer, Shelley A. Phelan. Peroxiredoxin induction in breast 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 1245. doi:10.1158/1538-7445.AM2015-1245
Serum NT pro-BNP and individual genetic polymorphisms as predictors of trastuzumab-related cardiotoxicity.
Authors: S. Goel, J. Lynch, L. A. Chantrill, J. J. Rutovitz, B. Murray, E. A. Abdi, R. Bell, A. L. Sullivan, A. Goldrick, T. M. Hayes, G. Asghari, N. Wilcken, N. J. McCarthy, J. M. Beith
Journal: Journal of Clinical Oncology (2011)

TPS121 Background: Trastuzumab-related cardiotoxicity (TRC) may lead to premature cessation of adjuvant trastuzumab (T) amongst women with early stage HER2-positive breast cancer (ESHBC) and hence jeopardize their chance of cure. Its pathophysiology may relate to suppression of cardiomyocyte HER2 signalling or T-induced antibody-dependent cell mediated cytotoxicity (ADCC) against cardiomyocytes. Preclinical detection of TRC (ie. before a decline in left ventricular ejection fraction [LVEF] occurs) could facilitate earlier cardioprotective intervention and thus prevent interruption of T therapy. We aim to evaluate 3 biomarkers as potential preclinical predictors of TRC: (1) N-terminal pro-B-type natriuretic peptide (NT pro-BNP), a serum marker of increased LV wall tension which may rise prior to a decline in LVEF and is often elevated in women receiving T1; (2) polymorphisms in the Immunoglobulin G fragment C receptor (FCgR) genes, possible determinants of ADCC; (3) polymorphisms in the HER2 gene. Methods: Our multicentre prospective study is recruiting women with ESHBC receiving adjuvant anthracycline-based chemotherapy followed T for 52 weeks. Serum NT pro-BNP is measured at 4 timepoints: (1) baseline; (2) prior to first dose of T; (3) after 3 months of T; (4) after 6 months of T. Blood will also be analysed for the FCgRIIIa 158V/V and FCgRIIa 131H/H polymorphisms and the Ile655Val polymorphism (codon 655) in the HER2 gene. LVEF will be assessed at each timepoint, after 9 months and at completion of T. TRC is defined using criteria from major adjuvant T trials. Fisher’s exact test will determine if a doubling of baseline NT pro-BNP at timepoint 2, 3, or 4 predicts future TRC. In addition, logistic regression analyses will be used to develop models for levels of, or changes in, NT pro-BNP that predict for TRC. The predictive values, sensitivity, and specificity of the model with the strongest association with TRC will be calculated. Establishing the predictive value of a new model with +/- 10% accuracy will require a total of 200 patients, of which 115 have been enrolled. Clinicaltrials.gov registry number: NCT00858039. References: Goel S et al. J Clin Oncol 26: 2008 (May 20 suppl; abstr 20557).
Abstract 1531: Distinct roles of CXCR3 isoforms in promoting breast cancer stem-like cell properties and metastasis
Authors: Yanchun Li, Jocelyn C. Reader, Xinrong Ma, Namita Kundu, Tyler Kochel, Amy M. Fulton
Journal: Cancer Research (2015)

Abstract Growing evidence has demonstrated that the two major isoforms of chemokine receptor CXCR3 (CXCR3-A, CXCR3-B) both contribute to breast cancer pathogenesis and metastasis, however, in different ways. Understanding the relative contribution of each isoform is critical to optimize therapeutic strategies targeting CXCR3. Furthermore, the possible involvement of either CXCR3 isoform in cancer stem-like properties has not been reported. We examined the contribution of each isoform to metastasis using a panel of breast cell lines and a xenograft model of breast cancer; we also explored the role of major CXCR3 isoforms in the behavior of stem-like cells. CXCR3-A is more abundantly expressed than CXCR3-B in both primary human breast cancer tissue and in breast cancer cell lines. On the contrary, immortalized normal MCF-10A cells are CXCR3-B dominant. In basal-like MDA-MB-231 cells, CXCR3 ligand-stimulated proliferation is inhibited by CXCR3-B overexpression, with concurrent reduced activation of ERK1/2 and p38 kinases. Similarly, higher levels of CXCR3-B inhibit migration and invasion in vitro and metastasis in vivo. Accordingly, reduced CXCR3-B expression by gene-silencing enhances lung colonization in the xenograft model. Although exhibiting anti-proliferative and anti-metastatic roles in the non-stem cell population, CXCR3-B supports a cancer stem-like cell phenotype. In mammosphere-forming MDA-MB-231 cells, CXCR3-B is markedly up-regulated and mammosphere-forming capacity is further increased when overexpressing CXCR3-B. Likewise, soft agar growth is promoted by CXCR3-B overexpression. Accordingly, silencing CXCR3-B by shRNA inhibits stem-like properties. In conclusion, both isoforms need to be targeted to inhibit the pro-proliferative and pro-metastasis functions of CXCR3-A and the stem cell-promoting actions of CXCR3-B. Citation Format: Yanchun Li, Jocelyn C. Reader, Xinrong Ma, Namita Kundu, Tyler Kochel, Amy M. Fulton. Distinct roles of CXCR3 isoforms in promoting breast cancer stem-like cell properties and metastasis. [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 1531. doi:10.1158/1538-7445.AM2015-1531
Skeletal Scintigraphy in Radiation-Induced Fibrosis With Lymphedema
Authors: Jieqi Wang, Arya M. Iranmanesh, M. Elizabeth Oates
Journal: Clinical Nuclear Medicine (2016)

Despite increasing reliance on CT, MRI, and FDG PET/CT for oncological imaging, whole-body skeletal scintigraphy remains a frontline modality for staging and surveillance of osseous metastatic disease. We present a 54-year-old woman with metastatic breast cancer who received palliative external-beam radiation to the left ilium. Serial follow-up Tc-MDP bone scans demonstrated progressive soft-tissue uptake in her left lower extremity, extending from thigh to leg, with associated enlargement and skin thickening, consistent with lymphedema related to radiation-induced fibrosis. Correlative abdominopelvic CT scans confirmed fibrotic changes in the left thigh.
The Survey for Real-World-Practice &amp; Expectation of Asia-Pacific Physicians and Patients in Helicobacter Pylori Eradication (REAP-HP Survey)
Authors: Yoen-young Chuah, Deng-chyang Wu, Seng-kee Chuah, Jyh-chin Yang, Tzong-hsi Lee, Hong-zen Yeh, Chien-lin Chen, Yu-hwa Liu, Ping-i Hsu
Journal: Clinical Gastroenterology and Hepatology (2016)
13. Post-Symptomatic Intrathecal Infusion of AAV1 Results in Reversal of Storage Lesions Throughout the Brain in the Cat Model of Alpha-Mannnosidosis Leading To Clinical Improvement
Authors: Sea Young Yoon, Jessica H. Bagel, Manoj Kumar, Patricia A. O'Donnell, Harish Poptani, Charles H. Vite, John H. Wolfe
Journal: Molecular Therapy (2015)

Lysosomal storage diseases (LSDs) are debilitating neurometabolic disorders for which long-term effective therapies have not been developed for most. A critical barrier to progress in the successful treatment of LSDs is an approach that will allow sustained delivery of the missing lysosomal enzyme to the brain in a quantity sufficient to prevent neuropathology. Intrathecal injection of AAVs has been shown to mediate transduction of neuronal and glial cells in the brain and spinal cord of large animals, and it has recently been reported that AAV9 infusion into the cerebrospinal fluid (CSF) of MPS I cats improves histopathological lesions, but no evidence of improvement in clinical signs were reported. We tested the efficacy of post-symptomatic intrathecal delivery of AAV1 to the brain via the cisterna magna in alpha-mannosidosis (AMD) affected cats. Lysosomal alpha-mannosidase (LAMAN) activity in the CSF was consistently above untreated AMD cat control values. The lifespan of the treated cats was significantly extended compared to untreated cats and the onset of clinical symptoms were delayed and reduced in severity. We have previously shown that magnetic resonance spectroscopy (MRS) detects a large peak of accumulated oligosaccharides in the AMD brain of live animals, and it was significantly decreased in the treated cat brains. Post-mortem histopathology showed resolution of lysosomal storage lesions in most regions of the brain, including the cerebral cortex, caudate nucleus, hippocampus, cerebellum and choroid plexus, and LAMAN enzymatic activity was above levels of untreated tissues. Our results demonstrate that a single intrathecal injection of AAV1 expressing feline alpha-mannosidase gene (fMANB) into the CSF was able to mediate widespread neuronal transduction of the brain and meaningful clinical improvement. Thus, intrathecal gene delivery by AAV1 appears to be a viable strategy for a long lasting treatment for the whole brain in AMD and, based on the widespread gene distribution, should be applicable to many of the neurotropic LSDs as well as other neurogenetic disorders.
Hypoxic Hematopoietic Stem and Progenitor Cells Reside in Structurally Diverse Perivascular Niches in the Bone Marrow,
Authors: Cesar Nombela-Arrieta, Gregory Pivarnik, Beatrice Winkel, Brendan Harley, John E Mahoney, Jiayun Lu, Alexei Protopopov, Leslie E Silberstein
Journal: Blood (2011)
The Evolving Taxonomy of Health in Older Persons
Authors: William B. Applegate, Edward Ip
Journal: JAMA (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 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
Comparaison de différentes pinces à biopsies dans le diagnostic de l’œsophagite à éosinophiles
Journal: Endoscopy (2016)

L’œsophagite à éosinophiles est une entité assez récemment décrite et dont le diagnostic est histologique. Il est ainsi recommandé de multiplier les biopsies à différents niveaux dans l’œsophage pour augmenter les chances de poser ce diagnostic, en particulier en cas de dysphagie à endoscopie oesophagienne macroscopiquement normale.
Comparison and characterization of the major allergen parvalbumin from cod, carp and frog
Authors: Y. Ma, U. Griesmeier, M. Susani, M. Fernandez-Rivas, A. Knulst, P. Saxoni-Papageorgiou, M. Bublin, O. Scheiner, H. Breiteneder, H. Karin
Journal: Allergy (2007)
88. Structural Studies Into the Stability of Novel In Silico Reconstructed Ancestral AAV Vectors
Authors: Simon Pacouret, Heikki Turunen, Eva Plovie-Buys, Ru Xiao, Rajani Shelke, Yang Lin, Eric Zinn, Luk H. Vandenberghe
Journal: Molecular Therapy (2015)

Adeno-associated virus (AAV) vectors have emerged as therapy preferred clinical in vivo gene transfer system. Yet, their sensitivity to pre-existing immunity (PEI) and low carrying capacity remain major drawbacks that limit broad applications. We previously hypothesized and have shown that ancestral species of AAV, which we inferred using statistical and bio-informatic approaches, and generated synthetically, have reduced susceptibility to PEI. Here, our ambition was to study from a biophysical and structural perspective the evolutionary process of AAV using these novel reagents, and to develop correlates of those measures with virus and vector phenotypes. By the means of polyacrylamide gel electrophoresis, intrinsic fluorescence spectroscopy and differential scanning fluorescence, we derive the thermostability profiles of 6 contemporary AAV serotypes (AAV1, AAV2, AAV5, AAV8, AAV9, rh32.33) and 3 ancestral AAV serotypes, called Anc80, Anc81 and Anc82 and differing from AAV8 in VP1 protein sequence by 9.3%, 7.8% and 5.3%, respectively. A theoretical structure of Anc80L0065 VP3 monomer was derived by homology modeling and compared to the crystal structures of AAV2, AAV8 and rh32.33. Structural modeling indicates significant sequence and structure differences between ancestral and contemporary VP3 protein subunits in loops I, IV, VII and VIII, regions that were shown to be involved in antibody and cell receptor binding. Surprisingly, Anc80, Anc81 and Anc82 showed an increase in capsomer melting temperature of approximately 20°C in comparison to AAV8, while vector genome is accessible at lower temperatures. Evolutionary intermediates between Anc80 and AAV8 demonstrate unique melting properties that permit the identification of a limited set of capsid determinants to the thermodynamic stability of AAVs. Our reconstructed phylogeny of AAVs emerges as a relevant tool for sequence-function analysis of AAV vectors.
A randomized, noninferiority study of recombinant human G-CSF/human serum albumin fusion (CG-10639) and pegfilgrastim in breast cancer patients receiving myelosuppressive therapy.
Authors: O. Gladkov, V. Moiseyenko, I. N. Bondarenko, J. V. Shparyk, S. Barash, J. M. Herpst
Journal: Journal of Clinical Oncology (2011)

9083 Background: Teva’s CG-10639 is a long-acting recombinant human albumin-human granulocyte-colony stimulating factor under investigation to prevent chemotherapy-induced neutropenia. Similar to pegfilgrastim (PEGF), CG-10639 stimulates neutrophil and hematopoietic stem cell mobilization from bone marrow to peripheral blood. No clinically relevant immunogenicity with CG-10639 has been observed to date. The main objective of this study was to evaluate the safety and effectiveness of CG-10639 versus PEGF in breast cancer patients (BCA pts) receiving myelosuppressive therapy. Methods: This phase II/III study was a randomized, multi-center, active controlled trial in 334 BCA pts receiving doxorubicin/docetaxel (DOX/DOC). The study included a pilot dose escalation phase to identify two CG-10639 doses with similar effects to PEGF (6mg), and a main phase powered for efficacy (non-inferiority). During the pilot phase, patients were randomized to receive CG-10639 30mg or PEGF one day after DOX/DOC followed by additional cohorts receiving CG-10639 40mg, 50mg. The main phase of the study used a randomized, 3-arm parallel design comparing two doses of CG-10639 and PEGF following DOX 60mg/m2 and DOC 75mg/m2 IV on day 1 for up to four 21-day cycles. The primary endpoint was the duration of severe neutropenia (DSN) during cycle 1 in days (d). Results: In the pilot phase (n=78) DSN, secondary efficacy parameters and safety were similar across all treatments. CG-10639 40mg and 50mg doses were selected for further investigation. In the main phase (n=256), there were no statistically significant differences in mean DSN between CG-10639 40mg (1.0d), CG-10639 50mg (1.3d), and PEGF (1.2d) in Cycle 1. In each cycle, efficacy was comparable based on ANC nadir and recovery, the incidence and duration of Grade 3 or 4 neutropenia, and the incidence of febrile neutropenia. The type and frequency of treatment emergent AEs were similar across treatment groups. Conclusions: These results support the conclusion that CG-10639 is non-inferior to PEGF based on mean DSN in BCA pts receiving myelosuppressive therapy. The overall safety profile was similar for CG-10639 and PEGF. A phase III, confirmatory study comparing CG-10639 40mg to PEGF 6mg is underway.
Toll-Like Receptor 3 Is a Mediator of the Innate Immune Response to Cytomegalovirus in Immature Dendritic Cells.
Authors: Hermann Einsele, Michael Bonin, Florian Gebhardt, Tobias Kessler, Susanne Riegler, Ziad Haddad, Holger Hebart, Juergen Loeffler
Journal: Blood (2004)
Arterial Wall Neovascularization:Potential Role in Atherosclerosis and Restenosis
Authors: Klaus Pels, Marino Labinaz, Edward R O'Brien
Journal: Circulation (1997)

Neointimal formation and arterial wall remodeling are pivotal causes of luminal narrowing in atherogenesis and restenosis. Arterial remodeling refers to a series of dynamic structural changes that arteries may undergo in response to various stimuli, including changes in blood flow and pressure, and acute injury. The biological mechanisms involved in arterial remodeling are poorly understood and are currently a main target for research. We have recently focused on the role of the arterial wall microcirculation (ie, vasa vasorum) in arterial remodeling after injury. In the past, a correlation between arterial wall neovascularization and the accumulation of arterial plaque has been documented; however, the dynamic role of these microvessels in arterial repair and luminal narrowing has not been examined. The type of arterial injury, the nature of the lesion that develops, and the arterial compartment in which angiogenesis occurs may determine the role of the vasa vasorum in arterial narrowing. In this review, we highlight the data that link arterial wall neovascularization with lesion formation and the process of arterial remodeling. (Jpn Circ J 1997; 61: 893 - 904)
Molecular signature of CD34+ hematopoietic stem and progenitor cells of patients with CML in chronic phase
Authors: E Diaz-Blanco, I Bruns, F Neumann, J C Fischer, T Graef, M Rosskopf, B Brors, S Pechtel, S Bork, A Koch, A Baer, U-P Rohr, G Kobbe, A von Haeseler, N Gattermann, R Haas, R Kronenwett
Journal: Leukemia (2007)
172. Correction of Profound Metabolic Impairments in MPS IIIB Mice by a Systemic rAAV9-hNAGLU Gene Delivery
Authors: Haiyan Fu, Aaron S. Meadows, F. Jason Duncan, Douglas M. McCarty
Journal: Molecular Therapy (2015)

Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease caused by deficiency in α-N-acetylglucosaminidase (NAGLU) leading to complex CNS and somatic pathology. This study was designed to characterize the metabolic impairments in MPS IIIB mice, and assess their responsiveness to effective gene therapy treatment. Using mass spectrometry targeting 361 metabolites, we detected significant decreases in 225 metabolites, and increases in 6, in serum from 7mo-old MPS IIIB mice, compared to wt mice. The metabolic disturbances in MPS IIIB mice emerge early, and involve virtually all major pathways of amino acid, peptide (58/102), carbohydrate (18/28), lipid (111/139), nucleotide (12/24), energy (2/9), vitamin and co-factors (11/16) and xenobiotics (11/28) metabolism. Notably, the reduced metabolites included 8 essential amino acids, Vitamins (C, E, B2, B6) and neurotransmitters (serotonin (5HT, glutamate, tryptophan, and N-acetyltyrosin). Importantly, the restoration of NAGLU activity with an IV injection of rAAV9-hNAGLU vector led to the efficient correction of these metabolic abnormalities, with 184 metabolites (79.7%) normalized, 6 (2.6%) partially corrected and 41 (17.7%) over-corrected. While the mechanisms are unclear, our data demonstrates that the lack of NAGLU activity triggers profound metabolic disturbances in MPS IIIB, leading to severely compromised functions in virtually all metabolic pathways. These metabolic impairments respond well to restoration of NAGLU activity using an effective gene therapy approach, supporting the biomarker potential of serum metabolomic profiles for MPS IIIB.