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Lin Li, Xiaotian Qi, Weili Sun, Hisham Abdel-Azim, Siyue Lou, Hong Zhu, Nemani V Prasadarao, Alice Zhou, Hiroyuki Shimada, Koichi Shudo, Yong-Mi Kim, Sajad Khazal, Qiaojun He, David Warburton, Lingtao Wu
Neutrophils generated by granulocyte colony-stimulating factor (GCSF) are functionally immature and, consequently, cannot effectively reduce infection and infection-related mortality in cancer chemotherapy-induced neutropenia (CCIN). Am80, a retinoic acid (RA) agonist that enhances granulocytic differentiation by selectively activating transcription factor RA receptor alpha (RARα), alternatively promotes RA-target gene expression. We found that in normal and malignant primary human hematopoietic specimens, Am80-GCSF combination coordinated proliferation with differentiation to develop complement receptor-3 (CR3)-dependent neutrophil innate immunity, through altering transcription of RA-target genes RARβ2, C/EBPε, CD66, CD11b, and CD18 This led to generation of functional neutrophils capable of fighting infection, whereas neutralizing neutrophil innate immunity with anti-CD18 antibody abolished neutrophil bactericidal activities induced by Am80-GCSF Further, Am80-GCSF synergy was evaluated using six different dose-schedule-infection mouse CCIN models...
October 13, 2016: EMBO Molecular Medicine
Adebayo Ogunniyi, Mabel Rodriguez, Sean Devlin, Nelly Adel, Heather Landau, David J Chung, Nikoletta Lendvai, Alexander Lesokhin, Guenther Koehne, Sham Mailankody, Neha Korde, Lilian Reich, Ola Landgren, Sergio Giralt, Hani Hassoun
Plerixafor (P), an agent that selectively and reversibly binds to the chemokine receptor CXCR4, has been approved in combination with G-CSF (P + G-CSF) for stem cell (SC) mobilization in patients with multiple myeloma (MM). The goal of this study was to determine the SC collection success rate of P + G-CSF using a clinically relevant outcome defined as the ability to collect at least 5 × 10(6) CD34(+) cells/kg to allow safely two transplants, and identify risk factors impacting SC mobilization...
October 13, 2016: Leukemia & Lymphoma
Vineet V Mishra, Sumesh Choudhary, Urmila Sharma, Rohina Aggarwal, Ritu Agarwal, Khushali Gandhi, Nilesh Goraniya
OBJECTIVE: To predict the effectiveness of granulocyte colony-stimulating factor (GCSF) in the treatment of persistent thin endometrium resistant to other treatments in frozen embryo transfer (FET) cycles. STUDY DESIGN: This is a hospital-based prospective study. PATIENTS: Thirty-five women with persistent thin endometrium (<7 mm) resistant to standard treatments were involved in this study. INTERVENTIONS: Intrauterine infusion of GCSF (300 mcg/1 ml) was done in patients with thin endometrium on day 14 of FET cycles, and their endometrial thicknesses were measured after 48 h of infusion...
October 2016: Journal of Obstetrics and Gynaecology of India
Matthew P Mulé, Gabriel N Mannis, Brent L Wood, Jerald P Radich, Jimmy Hwang, Nestor R Ramos, Charalambos Andreadis, Lloyd Damon, Aaron C Logan, Thomas G Martin, Christopher S Hourigan
We report here the largest study to date of adult patients with acute myeloid leukemia (AML) tested for measurable residual disease (MRD) at the time of autologous hematopoietic cell transplantation (auto-HCT). Seventy-two adult patients who underwent transplantation between 2004 and 2013 at a single academic medical center (University of California San Francisco) were eligible for this retrospective study based on availability of cryopreserved granulocyte colony-stimulating factor (GCSF)-mobilized autologous peripheral blood progenitor cell (PBPC) leukapheresis specimens ("autografts")...
November 2016: Biology of Blood and Marrow Transplantation
Gesa Weise, Claudia Pösel, Karoline Möller, Alexander Kranz, Nadine Didwischus, Johannes Boltze, Daniel-Christoph Wagner
Ischemic stroke elicits a prompt inflammatory response that is characterized by a well-timed recruitment of peripheral immune cells to the brain. Among these, monocytes play a particularly important, but multifaceted role and have been increasingly recognized to affect stroke outcome. Granulocyte colony stimulating factor (GCSF) is known for its immunosuppressive actions on mononuclear cells, but previous studies in the stroke field were mainly confined to its neuroprotective actions. Herein, we investigated whether GCSF affects post-stroke inflammation in a mouse model of focal brain ischemia by modulating monocyte responses...
August 11, 2016: Brain, Behavior, and Immunity
Sarita Rani Jaiswal, Shamsuz Zaman, Aditi Chakrabarti, Subrata Sen, Shashwata Mukherjee, Sneh Bhargava, Kunal Ray, Paul V O'Donnell, Suparno Chakrabarti
We carried out post-transplantation cyclophosphamide (PTCy)-based haploidentical peripheral blood stem cell transplantation in 51 patients with refractory/relapsed acute myeloid leukemia not in remission. The first 10 patients received nonmyeloablative conditioning followed by planned granulocyte colony-stimulating factor (G-CSF)-mobilized donor lymphocyte infusions (DLIs) on days 35, 60, and 90. No patient developed graft-versus-host disease (GVHD), but 90% had disease progression between 3 and 6 months. A subsequent 41 patients received myeloablative conditioning (MAC); the first 20 patients did not receive DLIs (MAC group) and the next 21 patients received G-CSF-mobilized DLIs (G-DLI) on days 21, 35, and 60 (MAC-DLI group)...
October 2016: Biology of Blood and Marrow Transplantation
Peter E Zage, Sarah B Whittle, Jason M Shohet
The neural crest is a population of cells in the vertebrate embryo that gives rise to a wide range of tissues and cell types, including components of the peripheral nervous system and the craniofacial skeleton as well as melanocytes and the adrenal medulla. Aberrations in neural crest development can lead to numerous diseases, including cancers such as melanoma and neuroblastoma. Cancer stem cells (CSCs) have been identified in these neural crest-derived tumors, and these CSCs demonstrate resistance to treatment and are likely key contributors to disease relapse...
July 18, 2016: Journal of Cellular Biochemistry
Ajay Kumar, Vinod Kumar, Vidya Rattan, Vivekanand Jha, Shalmoli Bhattacharyya
Dental tissue is emerging as a promising source of stem cells especially in nerve regeneration mainly due to their neural origin and ease of harvest. We isolated dental stem cells from three sources, namely, dental pulp (DPSCs), dental follicle (DFSCs), and apical papilla (SCAP), and explored the efficacy of each towards neural differentiation in comparison to bone marrow-derived stem cells. The neural differentiation potential was assessed by expression of various neural markers and neurosphere assay. We observed that DPSCs were inherently predisposed towards neural lineage...
July 15, 2016: Molecular Neurobiology
François Bocquet, Anaïs Loubière, Isabelle Fusier, Anne-Laure Cordonnier, Pascal Paubel
BACKGROUND: The expiry of patents for costly biologics is creating new momentum on the pharmaceutical market for biosimilars (copies of off-patent biologics) and paving the way for their development. However, little is known about the competitiveness of biosimilars versus their originators and other biologics belonging to the same therapeutic class. OBJECTIVE: The main goal of this study was to analyse the type of competition generated by the first biosimilars commercialised on key global biologic markets and to grasp their economic model...
November 2016: PharmacoEconomics
Diana Averbuch, Dan Engelhard, Anna Pegoraro, Simone Cesaro
Neutropenic patients with malignancies and hematopoietic stem cell transplant recipients are prone to severe infections. Reversal of neutropenia with granulocyte transfusion (GTX) from donors stimulated with GCSF with/without steroids aims to improve outcome of infection. Cochrane analysis of randomized controlled studies, however, failed to show reduced mortality following GTX in conjunction with antibiotics. Non-randomized studies published during the last 20 years produced a very broad spectrum of results...
July 5, 2016: Current Drug Targets
Christian Reichert, Remo Perozzo, Gerrit Borchard
We present here an approach to non-covalently combine an engineered model protein with a PEGylated peptide via coiled-coil binding. To this end a fusion protein of G-CSF and the peptide sequence (JunB) was created-one sequence of JunB was expressed at the N-terminal of GCSF. JunB is able to bind to the peptide sequence cFos, which was in turn covalently linked to a chain of poly(ethylene glycol) (PEG). The selected peptide sequences are leucine zipper motives from transcription factors and are known to bind to each other specifically by formation of a super secondary structure called coiled-coil...
September 10, 2016: International Journal of Pharmaceutics
Neh Nupur, Sumit Kumar Singh, Gunjan Narula, Anurag S Rathore
The biosimilar industry is witnessing an unprecedented growth with the newer therapeutics increasing in complexity over time. A key step towards development of a biosimilar is to establish analytical comparability with the innovator product, which would otherwise affect the safety/efficacy profile of the product. Choosing appropriate analytical tools that can fulfil this objective by qualitatively and/or quantitatively assessing the critical quality attributes (CQAs) of the product is highly critical for establishing equivalence...
October 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
Sarah Mousavi, Mina Dadpoor, Farzaneh Ashrafi
BACKGROUND: Granulocyte Colony Stimulating Factors (GCSF) is high-cost agents commonly recommended for primary and secondary prophylaxis of chemotherapy-induced neutropenia and febrile neutropenia. GCSFs have been shown to be beneficial in some patient subgroups, although they are probably overused in clinical settings. The American Society of Clinical Oncology (ASCO) guidelines summarize current data on the appropriate use of CSFs. The aim of this study was to assess and audit the use of GCSF in a tertiary care center according to the recommendation of ASCO guideline...
April 1, 2016: International Journal of Hematology-oncology and Stem Cell Research
Thomas Coventry, Faisal Azam
No abstract text is available yet for this article.
June 1, 2016: Clinical Medicine: Journal of the Royal College of Physicians of London
Ming-Feng Liao, Shin-Rung Yeh, Ai-Lun Lo, Po-Kuan Chao, Yun-Lin Lee, Yu-Hui Hung, Kwok-Tung Lu, Long-Sun Ro
Several studies have shown that the mu opioid receptor (MOR) located in the peripheral nerves can be activated after nerve injury and that it attenuates peripheral nociceptive signals to the spinal dorsal horn. Various cytokines and phosphorylated-p38 (p-p38) activation in the dorsal horn also play an important role in neuropathic pain development. Granulocyte-colony stimulating factor (GCSF) is a growth factor that can stimulate granulocyte formation and has been shown to exert an analgesic effect on neuropathic pain through recruiting opioid-containing leukocytes to the injured nerve...
2016: Scientific Reports
Tarik Catic, Alma Mekic-Abazovic, Samra Sulejmanovic
Febrile neutropenia is common chemotherapy complication significantly impacting patient's outcomes, quality of life and costs, too. Febrile neutropenia (FN) often leads to hospitalization, the need for intravenous antibiotics and use of granulocyte colony-stimulating factors (GCSF) in order to avoid its complications. Cost of febrile neutropenia is well described in literature, but no study has been performed in Bosnia and Herzegovina. We have conducted observational cohort study with aim to describe and present costs of FN treatment from payers' (provider's) perspective...
April 2016: Materia Socio-medica
L Bozzetto, G Annuzzi, M Ragucci, O Di Donato, G Della Pepa, G Della Corte, E Griffo, G Anniballi, A Giacco, M Mancini, A A Rivellese
BACKGROUND AND AIMS: The role of the different factors associated with fatty liver is still poorly defined. We evaluated the relationships between liver fat content (LF) and metabolic, inflammatory and nutritional factors in a homogeneous cohort of individuals at high cardio-metabolic risk. METHODS AND RESULTS: In 70 individuals with high waist circumference and at least one more criterion for metabolic syndrome enrolled in a nutritional intervention study, LF was evaluated at baseline by hepatic/renal echo intensity ratio (H/R), together with dietary habits (7-day dietary record), insulin sensitivity and β-cell function (fasting and OGTT-derived indices), fasting and postprandial plasma GLP-1 and lipoproteins, and plasma inflammatory markers...
July 2016: Nutrition, Metabolism, and Cardiovascular Diseases: NMCD
Saggere Muralikrishna Shasthry, Shiv Kumar Sarin
The burden of alcoholic liver disease has rapidly grown in the past two decades and is expected to increase further in the coming years. Alcoholic hepatitis, the most florid presentation of alcoholic liver disease, continues to have high morbidity and mortality, with significant financial and healthcare burden with limited treatment options. Steroids remain the current standard of care in severe alcoholic hepatitis in carefully selected patients. No specific treatments are available for those patients who are steroid ineligible, intolerant or unresponsive...
April 21, 2016: World Journal of Gastroenterology: WJG
Yeganeh Talebkhan, Tannaz Samadi, Armin Samie, Farzaneh Barkhordari, Mohammad Azizi, Vahid Khalaj, Esmat Mirabzadeh
BACKGROUND AND OBJECTIVES: During past decades Hansenula polymorpha has attracted global attention for the expression of recombinant proteins due to its high growth rate, minimal nutritional porequirements and use of methanol as a low cost inducer. MATERIALS AND METHODS: The corresponding nucleotide sequences for the expression of heterologous genes in Hansenula poylmorpha were extracted and assembled in an E. coli vector. The constructed expression cassette included formate dehydrogenase promoter (pFMD), a secretory signal sequence, a multiple cloning site (MCS) and methanol oxidase (MOX) terminator...
February 2016: Iranian Journal of Microbiology
Gautam Damera, Tuyet-Hang Pham, Jianchun Zhang, Christine K Ward, Paul Newbold, Koustubh Ranade, Sanjay Sethi
PURPOSE: Activation of the interleukin-1β (IL-1β) signaling pathway has been implicated in COPD, but the proportion of COPD subjects whose disease is principally driven by activation of this pathway is poorly understood. In this study, we sought to differentiate an IL-1β-associated sputum signature from other inflammation-associated COPD phenotypes. METHODS: Luminex-multiplex assays were used to study IL-1β-mediated signature proteins within airway epithelium, smooth muscle, and vascular endothelial cell cultures...
June 2016: Lung
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