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https://www.readbyqxmd.com/read/29141152/tm-values-and-unfolded-fraction-can-predict-aggregation-rates-for-gcsf-variant-formulations-but-not-under-predominantly-native-conditions
#1
Mathew J Robinson, Paul Matejtschuk, Adrian F Bristow, Paul A Dalby
Protein engineering and formulation optimisation strategies can be taken to minimise protein aggregation in the biopharmaceutical industry. Short-term stability measures such as the mid-point transition temperature (Tm) for global unfolding provide convenient surrogates for longer-term (eg 2-year) degradation kinetics, with which to optimise 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...
November 15, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29027153/conflicting-data-on-the-incidence-of-leukopenia-and-neutropenia-after-heated-intraperitoneal-chemotherapy-with-mitomycin-c
#2
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...
October 12, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28941572/effects-of-neural-stem-cell-media-on-hypoxic-injury-in-rat-hippocampal-slice-cultures
#3
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
https://www.readbyqxmd.com/read/28899503/salicylate-based-phytopharmaceuticals-induce-adaptive-cytokine-and-chemokine-network-responses-in-human-fibroblast-cultures
#4
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
https://www.readbyqxmd.com/read/28875358/determination-of-critical-quality-attributes-for-a-biotherapeutic-in-the-qbd-paradigm-gcsf-as-a-case-study
#5
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
https://www.readbyqxmd.com/read/28870643/pegylated-gcsf-can-be-used-with-first-line-da-epoch-r-without-compromising-dose-intensity-safety-or-efficacy
#6
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...
August 14, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28744022/granulocyte-colony-stimulating-factor-gcsf-fused-with-fc-domain-produced-from-e-coli-is-less-effective-than-polyethylene-glycol-conjugated-gcsf
#7
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
https://www.readbyqxmd.com/read/28721592/construction-purification-and-characterization-of-a-homodimeric-granulocyte-colony-stimulating-factor
#8
Gitana Mickiene, Indre Dalgediene, Zilvinas Dapkunas, Gintautas Zvirblis, Henrikas Pesliakas, Algirdas Kaupinis, Mindaugas Valius, Edita Mistiniene, Milda Pleckaityte
Granulocyte colony-stimulating factor (G-CSF) has found widespread clinical application, and modified forms with improved biopharmaceutical properties have been marketed as well. PEGylation, the covalent modification of G-CSF with polyethylene glycol (PEG), has a beneficial effect on drug properties, but there are concerns connected to the immunogenicity of PEGylated compounds and bioaccumulation of the synthetic polymer. To overcome challenges connected with chemical modifications, we developed fusion proteins composed of two G-CSF molecules connected via different peptide linkers...
October 2017: Molecular Biotechnology
https://www.readbyqxmd.com/read/28715614/intraperitoneal-administration-of-adipose-tissue-derived-stem-cells-for-the-rescue-of-retinal-degeneration-in-a-mouse-model-via-indigenous-cntf-up-regulation-by-il-6
#9
Jeong Hoon Heo, Jung Ae Yoon, Eun Kyung Ahn, Hyun Kim, Sang Hwa Urm, Chul Oh Oak, Byeng Chul Yu, Sang Joon Lee
As the world's population begins to age, retinal degeneration is an increasing problem, and various treatment modalities are being developed. However, there have been no therapies for degenerative retinal conditions that are not characterized by neovascularization. We investigated whether transplantation of mouse adipose tissue-derived stem cells (mADSC) into the intraperitoneal space has a rescue effect on NaIO3 -induced retinal degeneration in mice. In this study, mADSC transplantation recovered visual function and preserved the retinal outer layer structure compared to the control group without any integration of mADSC into the retina...
July 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28713871/immune-dysfunctionality-of-replicative-senescent-mesenchymal-stromal-cells-is-corrected-by-ifn%C3%AE-priming
#10
Raghavan Chinnadurai, Devi Rajan, Spencer Ng, Kenneth McCullough, Dalia Arafat, Edmund K Waller, Larry J Anderson, Greg Gibson, Jacques Galipeau
Industrial-scale expansion of mesenchymal stromal cells (MSCs) is often used in clinical trials, and the effect of replicative senescence on MSC functionality is of mechanistic interest. Senescent MSCs exhibit cell-cycle arrest, cellular hypertrophy, and express the senescent marker β-galactosidase. Although both fit and senescent MSCs display intact lung-homing properties in vivo, senescent MSCs acquire a significant defect in inhibiting T-cell proliferation and cytokine secretion in vitro. IFNγ does not upregulate HLA-DR on senescent MSCs, whereas its silencing did not reverse fit MSCs' immunosuppressive properties...
April 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/28700465/alemtuzumab-versus-antithymocyte-globulin-induction-therapies-in-kidney-transplantation-patients-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#11
REVIEW
Jianming Zheng, Wenli Song
Alemtuzumab (ALEM) is widely used as an induction therapy for organ transplantation, and numerous randomized controlled trials (RCTs) have been published to evaluate its efficacy and safety in kidney transplantation as compared with antithymocyte globulin (ATG). The purpose of this study was to compare the benefits and safety of ALEM with those of ATG for induction therapy.A systematic literature search in three electronic databases, including PubMed, EmBase, and Cochrane Library, since inception through October 2016, was conducted to identify potential RCTs for inclusion...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28689389/is-there-additive-therapeutic-effect-when-gcsf-combined-with-adipose-derived-stem-cell-in-a-rat-model-of-acute-spinal-cord-injury
#12
Joongkee Min, Jeong Hoon Kim, Kyoung Hyo Choi, Hyung Ho Yoon, Sang Ryong Jeon
OBJECTIVE: Functional and neural tissue recovery has been reported in many animal studies conducted with stem cells. However, the combined effect of cytokines and stem cells has not yet been adequately researched. Here, we analyzed the additive effects of granulocyte colony-stimulating factor (GCSF) on adipose-derived stem cells (ADSCs) infusion in the treatment of acute spinal cord injury (SCI) in rats. METHODS: Four days after intrathecal infusion tubes implantation in Sprague-Dawley rats, SCI was induced with an infinite horizon impactor...
July 2017: Journal of Korean Neurosurgical Society
https://www.readbyqxmd.com/read/28660351/moxifloxacin-versus-levofloxacin-or-ciprofloxacin-prophylaxis-in-acute-myeloid-leukemia-patients-receiving-chemotherapy
#13
Daniel J Przybylski, David J Reeves
PURPOSE: Patients receiving intensive chemotherapy regimens are at high risk for infectious complications due to prolonged neutropenia and hospital stay. Fluoroquinolone antibiotics, mainly levofloxacin and ciprofloxacin, are the mainstay of prophylactic therapy for these patients. There is limited data regarding the utilization of other quinolone antibiotics including moxifloxacin in this setting. METHODS: A retrospective chart review was completed comparing the use of prophylactic moxifloxacin to that of levofloxacin or ciprofloxacin during periods of prolonged neutropenia...
December 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28589070/agranulocytosis-sequelae-of-chronic-cocaine-use-case-series-and-literature-review
#14
Roma Srivastava, Maira Rizwan, Muhammad Omer Jamil, Palaniandy Kogulan, Donna Salzman
Agranulocytosis is a rare condition with a reported incidence ranging from one to five cases per million population per year. Most commonly, agranulocytosis is secondary to chemotherapeutic agents, however, other medications have also been associated with it. An immune mediated destruction of circulating granulocytes and/or granulocyte precursors secondary to drug-dependent or drug-induced antibodies is the postulated mechanism. Agranulocytosis has also been reported secondary to recreational drug use...
May 3, 2017: Curēus
https://www.readbyqxmd.com/read/28484308/anti-inflammatory-effects-of-the-mediterranean-diet-in-the-early-and-late-stages-of-atheroma-plaque-development
#15
Rosa Casas, Mireia Urpi-Sardà, Emilio Sacanella, Sara Arranz, Dolores Corella, Olga Castañer, Rosa-María Lamuela-Raventós, Jordi Salas-Salvadó, José Lapetra, Maria P Portillo, Ramón Estruch
Objective. To evaluate the long-term effects of a Mediterranean diet (MeDiet) intervention on the plasma concentrations of inflammatory and plaque stability-related molecules in elderly people at high risk for cardiovascular disease. Design and Setting. 66 participants from primary care centers affiliated with the Hospital Clinic of Barcelona were randomized into 3 groups: MeDiet plus extra virgin olive oil (EVOO) or nuts and a low-fat diet (LFD). At baseline and at 3 and 5 years, we evaluated the changes in the plasma concentrations of 24 inflammatory biomarkers related to the different stages of the atherosclerotic process by Luminex®...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28456908/use-of-prophylactic-growth-factors-and-antimicrobials-in-elderly-patients-with-cancer-a-review-of-the-medicare-database
#16
Romina Sosa, Shuling Li, Julia T Molony, Jiannong Liu, Scott Stryker, Allan J Collins
PURPOSE: Growth factors and antimicrobials can reduce complications of chemotherapy-induced myelosuppression. Their prophylactic use in elderly patients is important given the associated comorbidity in this age group. There is a developing trend by payers to include supportive care agents in chemotherapy care bundles, which could affect clinical practice. We examined whether the febrile neutropenia (FN) risk categories can be used to describe utilization in the Centers for Medicare & Medicaid fee-for-service system in older adults...
April 29, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28408239/protective-responses-of-two-paralogs-of-granulocyte-colony-stimulating-factor-gcsf-in-rock-bream-oplegnathus-fasciatus-during-bacterial-and-viral-infection
#17
Joseph Jeswin, Ji-Min Jeong, Jae-Dong Shim, Jin-Sol Bae, Chan-Il Park
Granulocyte colony stimulating factor (GCSF) has a key role in the production of neutrophilic granulocytes during normal hematopoietic development and release of neutrophils into the blood circulation. In this study we have identified and characterized two paralogs of GCSF (RbGCSF) in rock bream. Although RbGCSF-1 and RbGCSF-2 share low sequence conservation, its domains and protein structure still share significant similarity. Basal levels of RbGCSF-1 gene expression was high in peripheral blood leukocytes (PBLs), spleen and intestine whereas the RbGCSF-2 was highly expressed in PBLs and kidney, of healthy animals...
April 10, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28408238/novel-roles-for-podocalyxin-in-regulating-stress-myelopoiesis-rap1a-and-neutrophil-migration
#18
Pan Li, Aldona A Karaczyn, Rose McGlauflin, Amanda J Favreau-Lessard, Edward Jachimowicz, Calvin P Vary, Kailin Xu, Don M Wojchowski, Pradeep Sathyanarayana
Podocalyxin (Podxl) is a CD34 orthologue and cell surface sialomucin reported to have roles in renal podocyte diaphragm slit development; vascular cell integrity; and the progression of blood, breast, and prostate cancers. Roles for Podxl during nonmalignant hematopoiesis, however, are largely undefined. We have developed a Vav-Cre Podxl knockout (KO) mouse model, and report on novel roles for Podxl in governing stress myelopoiesis. At steady state, Podxl expression among hematopoietic progenitor cells was low level but was induced by granulocyte colony-stimulating factor (G-CSF) in myeloid progenitors and by thrombopoietin in human stem cells...
June 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28364041/galectin-3-interacts-with-the-cell-surface-glycoprotein-cd146-mcam-muc18-and-induces-secretion-of-metastasis-promoting-cytokines-from-vascular-endothelial-cells
#19
Florent Colomb, Weikun Wang, Deborah Simpson, Mudaser Zafar, Robert Beynon, Jonathan M Rhodes, Lu-Gang Yu
The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model. This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28337172/bone-marrow-derived-cell-accumulation-in-the-spinal-cord-is-independent-of-peripheral-mobilization-in-a-mouse-model-of-amyotrophic-lateral-sclerosis
#20
Kyle Peake, John Manning, Coral-Ann Lewis, Kevin Tran, Fabio Rossi, Charles Krieger
Bone marrow-derived cells (BMDCs) are capable of migrating across the blood-brain barrier (BBB) and accumulating in the central nervous system (CNS) when transplanted into recipients conditioned with whole-body irradiation or chemotherapy. We used the chemotherapeutic agents busulfan and treosulfan to condition recipient mice for transplantation with bone marrow (BM) cells isolated from donor mice ubiquitously expressing green fluorescent protein. We attempted to increase the accumulation of BMDCs in the CNS by mobilization of BMDCs using either, or both, granulocyte colony-stimulating factor (GCSF) or plerixafor (AMD3100)...
2017: Frontiers in Neurology
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