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Jung-Rok Lee, Iris Appelmann, Cornelius Miething, Tyler O Shultz, Daniel Ruderman, Dokyoon Kim, Parag Mallick, Scott W Lowe, Shan X Wang
Cancer proteomics is the manifestation of relevant biological processes in cancer development. Thus, it reflects the activities of tumor cells, host-tumor interactions, and systemic responses to cancer therapy. To understand the causal effects of tumorigenesis or therapeutic intervention, longitudinal studies are greatly needed. However, most of the conventional mouse experiments are unlikely to accommodate frequent collection of serum samples with a large enough volume for multiple protein assays towards single-object analysis...
2018: Theranostics
Anja Sophie Schmid, Diana Tintor, Dario Neri
Neutrophils can strongly influence disease activity in cancer and in chronic inflammation. Here, we report for the first time the construction and characterization of antibody-fusion proteins featuring granulocyte-colony stimulating factor and interleukin-3 as payloads capable of enhancing neutrophil activity and a novel antibody-interleukin-4 fusion protein with neutrophil inhibitory potential. We used the F8 antibody specific to the alternatively-spliced extra domain A (EDA) of fibronectin as a targeting agent, since the cognate antigen is strongly upregulated in diseases characterized by angiogenesis...
February 10, 2018: Journal of Biotechnology
Virendra Singh, Amarjit Keisham, Ashish Bhalla, Navneet Sharma, Ritesh Agarwal, Ratiram Sharma, Akash Singh
BACKGROUND & AIMS: Patients with alcoholic hepatitis (AH) have high mortality, so new therapies are needed. Administration of granulocyte colony stimulating factor (GCSF) increases survival times of patients with AH. It is not known whether addition of N-acetyl cysteine (NAC) to GCSF could further increase survival time. We performed a randomized controlled pilot study to compare the efficacy of standard medical therapy with pentoxifylline to treatment with a combination of GCSF and standard medical therapy as well as to the combination of NAC, GCSF, and standard medical therapy in patients with severe AH...
January 29, 2018: Clinical Gastroenterology and Hepatology
Thiago Cabral, Luiz H Lima, Luiz Guilherme M Mello, Júlia Polido, Éverton P Correa, Akiyoshi Oshima, Jimmy Duong, Pedro Serracarbassa, Caio V Regatieri, Vinit B Mahajan, Rubens Belfort
Purpose: To evaluate the expression of 19 angiogenic biomarkers in the aqueous humor before and after intravitreal bevacizumab injection (IVB) in eyes with neovascular age-related macular degeneration (AMD). Design: Prospective, noncomparative, interventional case series. Participants: Twenty-three eyes of 23 treatment-naïve patients with choroidal neovascularization (CNV) secondary to neovascular AMD. Methods: Eyes were diagnosed with CNV secondary to neovascular AMD and were treated with 3 monthly IVBs...
January 2018: Ophthalmology Retina
Vivek Dharwal, Amarjit S Naura
COPD is associated with high morbidity and mortality and no effective treatment is available till date. We have previously reported that PARP-1 plays an important role in the establishment of airway inflammation associated with asthma and ALI. In the present work, we have evaluated the beneficial effects of PARP-1 inhibition on COPD pathogenesis utilizing elastase induced mouse model of the disease. Our data show that PARP-1 inhibition by olaparib significantly reduced the elastase-induced recruitment of inflammatory cells particularly neutrophils in the lungs of mice when administered at a dose of 5 mg/kg b...
January 30, 2018: Biochemical Pharmacology
Yohannes A Mebratu, Yohannes Tesfaigzi
Respiratory syncytial virus (RSV) is associated with enhanced progression of chronic obstructive pulmonary disease (COPD) and COPD exacerbations. However, little is known about the role of IL-17 in RSV-induced lung injury. We first investigated the role of RSV infection in enhancing mucous cell hyperplasia and airspace enlargement in the lungs of mice injured with elastase and lipopolysaccharide (E/LPS). Mice injured with E/LPS had an enhanced and prolonged neutrophilic response to RSV that was associated with decreased levels of type I IFN and increased levels of IL-17, IL-23, CXCL-1, GCSF and CXCL-5 and MMP-9...
January 9, 2018: American Journal of Respiratory Cell and Molecular Biology
Bülent Erdemli, Emre Anıl Özbek, Kerem Başarir, Zeynep Ceren Karahan, Duygu Öcal, Derya Biriken
OBJECTIVE: The aims of this study were 1) to identify the level of inflammatory biomarkers interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-17, C-reactive protein (CRP), granulocyte colony-stimulating factor (GCSF), ferritin, and tumor necrosis factor (TNF)-α in serum and synovial fluid samples of patients who underwent revision arthroplasty surgery; 2) to establish the relationship between serum and synovial fluid levels; 3) to determine if any of the 11 genetic polymorphisms of TNFα, IL-1, IL-6, IL-8, IL-17, and GCSF on the encoding genes was associated with periprosthetic joint infection (PJI)...
January 2, 2018: Acta Orthopaedica et Traumatologica Turcica
Amir Daei Farshchi Adli, Rana Jahanban-Esfahlan, Khaled Seidi, Sonia Samandari-Rad, Nosratollah Zarghami
Vascular disrupting agents (VDAs), a group of cancer remedies, can cause a specific and irreversible destruction of established tumor vessels, and the complete halt of blood flow in the tumor. DMXAA(ASA404) or Vadimezan, a flavone-acetic acid-based drug is the most promising VDAs that induces a rapid shutdown of blood flow in tumors but not in normal tissue. The exact mechanism of vascular disruption is unknown; however proposed direct and indirect mechanisms of action for DMXAA comprises: i) inducing apoptosis in endothelial cells; ii) hemorrhagic necrosis and ischemia in tumor; iii) release of serotonin (5-HT); vi) stimulation of innate immune system; v) production of inflammatory cytokines e...
December 30, 2017: Chemical Biology & Drug Design
John Wong, Lisa T Tran, Kaari A Lynch, Lisa J Wood
Cytotoxic chemotherapy can induce a systemic inflammatory response which has been proposed to be an underlying mechanism of cancer treatment related fatigue. Dexamethasone, a synthetic glucocorticoid that has potent anti-inflammatory effects, is incorporated into chemotherapy regimens to prevent chemotherapy-induced nausea and vomiting (CINV). The purpose of this study was to determine whether by suppressing cytotoxic chemotherapy-induced inflammation, dexamethasone could ameliorate chemotherapy induced fatigue/lethargy in tumor free mice...
January 2, 2018: Cancer Biology & Therapy
Joseph R Scalea, Young Suk Lee, Eduardo Davila, Jonathan S Bromberg
Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells of the myeloid lineage upregulated by mediators of inflammation, such as IL-2, granulocyte colony-stimulating factor, and S100A8/A9. These cells have been studied extensively by tumor biologists. Because of their robust immunosuppressive potential, MDSCs have stirred recent interest among transplant immunologists as well. MDSCs inhibit T-cell responses through, among other mechanisms, the activity of arginase-1 and inducible nitric oxide synthase, and the expansion of T regulatory cells...
March 2018: Transplantation
Pere Gascón, Andriy Krendyukov, Nadja Höbel, Matti Aapro
OBJECTIVE: Prospective data on the use of granulocyte-colony-stimulating factor (G-CSF) in non-Hodgkin's lymphoma and its aggressive subtypes, including diffuse large B-cell lymphoma (DLBCL), are limited. MONITOR-GCSF is a pan-European, multicenter, prospective, observational study aiming to describe treatment patterns and clinical outcomes in patients receiving biosimilar filgrastim in the prophylaxis of chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN). METHODS: This analysis describes patient characteristics, treatment patterns, and outcomes for 245 patients with stage 3 or 4 DLBCL receiving ≤6 chemotherapy cycles as part of MONITOR-GCSF study, including patients aged ≥65 years and ≥70 years...
March 2018: European Journal of Haematology
Andrew Fiore-Gartland, Angela Panoskaltsis-Mortari, Anna A Agan, Anushay J Mistry, Paul G Thomas, Michael A Matthay, Tomer Hertz, Adrienne G Randolph
Rationale: Effective immunomodulatory therapies for children with life-threatening "cytokine storm" triggered by acute influenza infection are lacking. Understanding the immune profiles of children progressing to severe lung injury and/or septic shock could provide insight into pathogenesis. Objectives: To compare the endotracheal and serum cytokine profiles of children with influenza-related critical illness and to identify their associations with severe influenza-associated complications...
2017: Frontiers in Immunology
Stefano Rossetti, Michael J Anauo, Nicoletta Sacchi
RUNX1, a master transcription factor of hematopoiesis, was shown to orchestrate both cell proliferation and differentiation during granulopoiesis by regulating microRNAs (miRs). In this study, taking advantage of the miR-ON reporter system, we monitored first, how the granulocyte colony stimulation factor (GCSF) temporally modulates the concomitant level variation of miR-221 and one of its prototypic targets, the stem cell factor receptor KIT, in single 32DmiR-ON-221 myeloblasts expressing wild type RUNX1. Second, with the same reporter system we assessed how these temporal dynamics are affected by the t(8;21)(q22;q22) acute myelogenous leukemia mutant RUNX1-MTG8 (RM8) in single 32D-RM8miR-ON-221 myeloblasts...
October 17, 2017: Oncotarget
Mathew J Robinson, Paul Matejtschuk, Adrian F Bristow, Paul A Dalby
Protein engineering and formulation optimization strategies can be taken to minimize protein aggregation in the biopharmaceutical industry. Short-term stability measures such as the midpoint transition temperature (Tm ) for global unfolding provide convenient surrogates for longer-term (e.g., 2-year) degradation kinetics, with which to optimize formulations on practical time-scales. While successful in some cases, their limitations have not been fully evaluated or understood. Tm values are known to correlate with chemical degradation kinetics for wild-type granulocyte colony stimulating factor (GCSF) at pH 4-5...
January 2, 2018: Molecular Pharmaceutics
Yael Feferman, Shanel Bhagwandin, Joseph Kim, Samantha N Aycart, Daniela Feingold, Daniel M Labow, Umut Sarpel
BACKGROUND: During heated intraperitoneal chemotherapy (HIPEC), neutropenia rates of 20 to 40% have been reported when mitomycin C (MMC) is dosed by weight or body surface area (BSA). This study investigated the authors' HIPEC experience using a fixed 40-mg dose of MMC, per consensus guidelines, and analyzed predictors for severe leukopenia and neutropenia. METHODS: Patients who underwent MMC-HIPEC from 2007 to 2016 at a single tertiary care center were retrospectively reviewed...
December 2017: Annals of Surgical Oncology
Na Mi Lee, Soo Ahn Chae, Hong Jun Lee
Neonatal hypoxic-ischemic brain injuries cause serious neurological sequelae, yet there is currently no effective treatment for them. We hypothesized that neurotrophic factors released into the medium by stem cells could supply hypoxia-damaged organotypic hippocampal slice cultures with regenerative abilities. We prepared organotypic slice cultures of the hippocampus of 7-day-old Sprague-Dawley rats based on the modified Stoppini method; slices were cultured for 14days in vitro using either Gahwiler's medium (G-medium) or stem cell-conditioned medium (S-medium) as culture medium...
December 15, 2017: Brain Research
Gudrun Ulrich-Merzenich, Frederik Hartbrod, Olaf Kelber, Jürgen Müller, Anna Koptina, Heike Zeitler
BACKGROUND: Cytokines and chemokines (CC) play a central role in immunoregulatory and inflammatory processes. Neutralising antibodies for single proinflammatory cytokines have developed into a powerful, though expensive and not always curative therapeutic strategy for severe diseases. Considering the redundancy of CC functions, network (N) rather than single target approaches are essential. Phytopharmaceuticals, common adjuvant therapies, are known modulators of a broad spectrum of CCs, but as complex mixtures with multiple targets they have not been systematically investigated...
October 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Sumit K Singh, Deepak Kumar, Anurag S Rathore
Estimating impact of the various product-related variants and impurities on a biotherapeutic's safety and efficacy is an essential requirement in the quality by design paradigm. In view of the limited role that clinical studies offer in this regard, we demonstrate a preclinical approach to achieve this for granulocyte colony-stimulating factor (GCSF). While our repeated-dose toxicity data suggest that these variants do not elicit any adverse effects or histopathological changes, aggregated GCSF impurity caused sluggishness in animal behavior manifested by a possible muscular injury...
November 2017: AAPS Journal
Prathima Reddy, Sandra Kanan, Andrew Cowan, Houston Warren, Brian Till, Mazyar Shadman, Ryan Cassaday, Oliver Press, Andrei Shustov, Ajay Gopal, Stephen D Smith
INTRODUCTION: Infusional da-EPOCH-R (dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab) is a dose-intensified regimen with a potential role in treating high-risk subtypes of aggressive B-cell non-Hodgkin lymphoma (B-NHL). Studies of da-EPOCH-R use daily injections of granulocyte colony-stimulating factor (GCSF) to tailor chemotherapy dosing, and whether 1-time administration of pegylated GCSF (peg-GCSF) is as efficacious has not been addressed...
December 2017: Clinical Lymphoma, Myeloma & Leukemia
Bich Hang Do, Hyo Jeong Kang, Jung-A Song, Minh Tan Nguyen, Sangsu Park, Jiwon Yoo, Anh Ngoc Nguyen, Grace G Kwon, Jaepyeong Jang, Mihee Jang, Sunju Lee, Seoungjun So, Seongrak Sim, Kyung Jin Lee, Mark J Osborn, Han Choe
Human granulocyte colony-stimulating factor (GCSF) is a well-known cytokine for neutropenia treatment. However, daily injections are required due to the short circulating half-life of the protein. To overcome this bottleneck, we fused GCSF with the Fc domain of IgG1 at the C terminus (GCSF-Fc) and with the maltose binding protein (MBP) tag at the N-terminus and expressed it as a soluble protein in the cytoplasm of E. coli. We also conjugated PEG aldehyde to GCSF to make PEG-GCSF. The bioactivities of GCSF-Fc and PEG-GCSF were similar to native GCSF using the mouse M-NFS-60 myelogenous leukemia cell line...
July 25, 2017: Scientific Reports
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