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https://www.readbyqxmd.com/read/27905003/new-agents-in-hsc-mobilization
#1
REVIEW
Mélanie J Domingues, Susan K Nilsson, Benjamin Cao
Mobilized peripheral blood (PB) is the most common source of hematopoietic stem cells (HSC) for autologous transplantation. Granulocyte colony stimulating factor (G-CSF) is the most commonly used mobilization agent, yet despite its widespread use, a considerable number of patients still fail to mobilize. Recently, a greater understanding of the interactions that regulate HSC homeostasis in the bone marrow (BM) microenvironment has enabled the development of new molecules that mobilize HSC through specific inhibition, modulation or perturbation of these interactions...
November 30, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27896627/n-11-c-methyl-amd3465-pet-as-a-tool-for-in-vivo-measurement-of-chemokine-receptor-4-cxcr4-occupancy-by-therapeutic-drugs
#2
S V Hartimath, M A Khayum, A van Waarde, R A J O Dierckx, E F J de Vries
PURPOSE: Chemokine receptor 4 (CXCR4) is overexpressed in many cancers and a potential drug target. We have recently developed the tracer N-[(11)C]methyl-AMD3465 for imaging of CXCR4 expression by positron emission tomography (PET). We investigated the pharmacokinetics of N-[(11)C]methyl-AMD3465 in rats bearing a C6 tumor and assessed whether the CXCR4 occupancy by the drug Plerixafor® can be measured with this PET tracer. PROCEDURE: A subcutaneous C6 tumor was grown in Wistar rats...
November 28, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27859332/patients-outcome-after-rescue-plerixafor-administration-for-autologous-stem-cell-mobilization-a-single-center-retrospective-analysis
#3
Silvia Spoerl, Robert Peter, Dagmar Wäscher, Katharina Götze, Mareike Verbeek, Christian Peschel, Angela M Krackhardt
BACKGROUND: Plerixafor is predominantly used for patients mobilizing inadequate stem cell numbers for autologous transplantation after stimulation with granulocyte-colony-stimulating factor (G-CSF). STUDY DESIGN AND METHODS: We here report on 300 patients undergoing stem cell mobilization with G-CSF, among them 36 poor mobilizers (CD34+ cell counts < 50 × 10(6) /L blood) receiving G-CSF alone and 49 receiving G-CSF in combination with plerixafor for rescue intervention...
November 18, 2016: Transfusion
https://www.readbyqxmd.com/read/27846612/effect-of-high-dose-plerixafor-on-cd34-cells-mobilization-in-healthy-stem-cell-donors-results-of-a-randomized-crossover-trial
#4
Jeremy Pantin, Enkhtsetseg Purev, Xin Tian, Lisa Cook, Theresa Donohue-Jerussi, Elena Cho, Robert Reger, Matthew Hsieh, Hanh Khuu, Gary Calandra, Nancy L Geller, Richard W Childs
Hematopoietic stem cells can be mobilized from healthy donors using single-agent plerixafor without G-CSF, and following allogeneic transplantation, can result in sustained donor derived hematopoiesis. However, when a single dose of plerixafor is administered at a conventional 240 mg/kg dose, approximately one third of donors will fail to mobilize the minimally acceptable dose of CD34+ cells needed for allogeneic transplantation. We conducted an open-label, randomized trial to assess the safety and activity of high-dose (480 mg/kg) plerixafor in CD34+ cell mobilization in healthy donors...
October 20, 2016: Haematologica
https://www.readbyqxmd.com/read/27826715/extracellular-molecules-in-hematopoietic-stem-cell-mobilisation
#5
REVIEW
Linda Bendall
Hematopoietic stem cells are a remarkable resource currently used for the life saving treatment, hematopoietic stem cell transplantation. Today, hematopoietic stem cells are primarily obtained from mobilized peripheral blood following treatment of the donor with the cytokine G-CSF, and in some settings, chemotherapy and/or the CXCR4 antagonist plerixafor. The collection of hematopoietic stem cells is contingent on adequate and timely mobilization of these cells into the peripheral blood. The use of healthy donors, particularly when unrelated to the patient, requires mobilization strategies be safe for the donor...
November 8, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27809841/pharmacological-targeting-of-cxcl12-cxcr4-signaling-in-prostate-cancer-bone-metastasis
#6
M Katie Conley-LaComb, Louie Semaan, Rajareddy Singareddy, Yanfeng Li, Elisabeth I Heath, Seongho Kim, Michael L Cher, Sreenivasa R Chinni
BACKGROUND: The CXCL12/CXCR4 axis transactivates HER2 and promotes intraosseous tumor growth. To further explore the transactivation of HER2 by CXCL12, we investigated the role of small GTP protein Gαi2 in Src and HER2 phosphorylation in lipid raft membrane microdomains and the significance of CXCR4 in prostate cancer bone tumor growth. METHODS: We used a variety of methods such as lipid raft isolation, invasion assays, an in vivo model of intratibial tumor growth, bone histomorphometry, and immunohistochemistry to determine the role of CXCR4 signaling in lipid raft membrane microdomains and effects of targeting of CXCR4 for bone tumor growth...
November 3, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27749622/plerixafor-mobilization-of-peripheral-blood-hematopoietic-progenitors-to-support-further-high-dose-chemotherapy-cycles-in-a-patient-with-germ-cell-tumor-relapsing-after-previous-tandem-high-dose-chemotherapy-and-hematopoietic-cell-transplantation-report-of
#7
Constantinos Miltiadous, Georgios K Dimitriadis, Pavlos Roditis, Christos Kosmas
Salvage high-dose chemotherapy (HDC) and autologous hematopoietic stem cell (HSC) transplantation represents a curative treatment option for patients with relapsed/refractory germ-cell tumors (GCTs). However, an appreciable proportion of these fail to mobilize adequate numbers of hematopoietic progenitors; thus, plerixafor is applied for that purpose. Limited data exist on remobilization of HSCs after previous autografting. Here, we report a unique case that had undergone successful previous tandem HDC for relapsed GCT, and 1 year later required remobilization of HSCs to support two further cycles of HDC after subsequent multiple relapses and refractoriness requiring various salvage regimens...
October 4, 2016: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27735212/upfront-use-of-plerixafor-and-granulocyte-colony-stimulating-factor-gcsf-for-stem-cell-mobilization-in-patients-with-multiple-myeloma-efficacy-and-analysis-of-risk-factors-associated-with-poor-stem-cell-collection-efficiency
#8
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
https://www.readbyqxmd.com/read/27731496/how-do-we-mobilize-and-collect-autologous-peripheral-blood-stem-cells
#9
Shan Yuan, Shirong Wang
Autologous stem cell transplantation (ASCT) with mobilized peripheral blood stem cells (PBSCs) has become a widely applied therapeutic approach for many hematologic and nonhematologic diseases. Adequate PBSC mobilization is critical to the success of ASCT. However, many factors can contribute to poor mobilization. Plerixafor is an effective yet costly adjunct agent that has been increasingly used to improve mobilization in a variety of diagnoses and clinical settings. However, to achieve both optimal cell collection yields and cost-effectiveness, the role of plerixafor in PBSC mobilization needs to be well defined in terms of triggers for initiating its use and criteria for monitoring response...
October 12, 2016: Transfusion
https://www.readbyqxmd.com/read/27697997/plerixafor-improves-primary-tumor-response-and-reduces-metastases-in-cervical-cancer-treated-with-radio-chemotherapy
#10
Naz Chaudary, Melania Pintilie, Salomeh Jelveh, Patricia Lindsay, Richard P Hill, Michael Milosevic
PURPOSE: There is an important need to improve the effectiveness of radio-chemotherapy (RTCT) for cervical cancer. The CXCL12/CXCR4 pathway can influence RT response by recruiting normal myeloid cells to the tumor microenvironment that in turn can exert radioprotective effects, and may promote metastases. The objective of this study was to explore the efficacy and toxicity of combining RTCT with CXCL12/CXCR4 inhibition in cervical cancer. EXPERIMENTAL DESIGN: CXCR4 expression was measured in 115 patients with cervical cancer...
October 3, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27634446/stem-cell-mobilizers-novel-therapeutics-for-acute-kidney-injury
#11
Yue Xu, Qiang Zhang, Song Zeng, Zijiang Zhang, Xiaopeng Hu
In the past decade, rapid developments in stem cell studies have occurred. Researchers have confirmed the plasticity of bone marrow stem cells and the repair and regeneration effects of bone marrow hematopoietic stem cells on solid organs. These findings have suggested the possibility of using bone marrow to repair and regenerate injured organs. Recent studies on the effects of granulocyte colony-stimulating factor (G-CSF) and Plerixafor (AMD3100) on mouse acute kidney injury models have confirmed that the use of bone marrow may be an effective therapeutic measure...
September 9, 2016: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/27617863/abc-transporters-and-nr4a1-identify-a-quiescent-subset-of-tissue-resident-memory-t-cells
#12
Chandra Sekhar Boddupalli, Shiny Nair, Simon M Gray, Heba N Nowyhed, Rakesh Verma, Joanna A Gibson, Clara Abraham, Deepak Narayan, Juan Vasquez, Catherine C Hedrick, Richard A Flavell, Kavita M Dhodapkar, Susan M Kaech, Madhav V Dhodapkar
Immune surveillance in tissues is mediated by a long-lived subset of tissue-resident memory T cells (Trm cells). A putative subset of tissue-resident long-lived stem cells is characterized by the ability to efflux Hoechst dyes and is referred to as side population (SP) cells. Here, we have characterized a subset of SP T cells (Tsp cells) that exhibit a quiescent (G0) phenotype in humans and mice. Human Trm cells in the gut and BM were enriched in Tsp cells that were predominantly in the G0 stage of the cell cycle...
October 3, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27612987/upfront-autologous-stem-cell-transplantation-for-newly-diagnosed-elderly-multiple-myeloma-patients-a-prospective-multicenter-study
#13
Laurent Garderet, Eric Beohou, Denis Caillot, Anne Marie Stoppa, Cyrille Touzeau, Marie Lorraine Chretien, Lionel Karlin, Philippe Moreau, Jean Fontan, Didier Blaise, Emmanuelle Polge, Mor Seny Gueye, Souhila Ikhlef, Zora Marjanovic, Myriam Labopin, Mohamad Mohty
The feasibility and efficacy of high-dose melphalan followed by autologous hematopoietic stem cell transplantation in newly diagnosed elderly patients with multiple myeloma was analyzed prospectively. Fifty-six multiple myeloma patients, aged 65 years or over, from 6 French centers were studied. The induction therapy was bortezomib-based in combination with dexamethasone and either thalidomide, cyclophosphamide or lenalidomide, for 4-6 cycles. Peripheral blood stem cells were collected after high-dose cyclophosphamide plus G-CSF or G-CSF alone, with plerixafor if needed...
November 2016: Haematologica
https://www.readbyqxmd.com/read/27578390/plerixafor-as-preemptive-strategy-results-in-high-success-rates-in-autologous-stem-cell-mobilization-failure
#14
Nina Worel, Gerhard Fritsch, Hermine Agis, Alexandra Böhm, Georg Engelich, Gerda C Leitner, Klaus Geissler, Karoline Gleixner, Peter Kalhs, Veronika Buxhofer-Ausch, Felix Keil, Gerhard Kopetzky, Viktor Mayr, Werner Rabitsch, Regina Reisner, Konrad Rosskopf, Reinhard Ruckser, Claudia Zoghlami, Niklas Zojer, Hildegard T Greinix
Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2...
August 31, 2016: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/27575003/chemokines-and-cocaine-cxcr4-receptor-antagonist-amd3100-attenuates-cocaine-place-preference-and-locomotor-stimulation-in-rats
#15
Jae Kim, Krista L Connelly, Ellen M Unterwald, Scott M Rawls
Plasma levels of the chemokine CXCL12 are elevated in mice following acute cocaine exposure and decreased in human cocaine abusers during withdrawal. CXCL12 is also one of the few chemokines located in the brain and can modulate dopamine transmission through activation of its receptor CXCR4. To assess a role for the CXCL12/CXCR4 system in behavioral effects of cocaine, we tested the hypothesis that AMD 3100 (Plerixafor), a CXCR4 antagonist, would inhibit conditioned place preference (CPP) and locomotor activation produced by cocaine...
August 26, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27542769/survival-and-proliferation-of-neural-progenitor-derived-glioblastomas-under-hypoxic-stress-is-controlled-by-a-cxcl12-cxcr4-autocrine-positive-feedback-mechanism
#16
Alexandra A Calinescu, Viveka Nand Yadav, Erica Carballo, Padma Kadiyala, Dustin Tran, Daniel Zamler, Robert Doherty, Maithreyi Srikanth, Pedro R Lowenstein, Maria G Castro
PURPOSE: One likely cause of treatment failure in glioblastoma is the persistence of glioma stem-like cells (GSLCs), highly resistant to therapies currently employed. We found that CXCL12 has highest expression in glioma cells derived from neural progenitor cells (NPCs). The development and molecular signature of NPC-derived GBMs were analyzed and the therapeutic effect of blocking CXCL12 was tested. EXPERIMENTAL DESIGN: Tumors were induced by injecting DNA into the lateral ventricle of neonatal mice, using the Sleeping Beauty transposase method...
August 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27536190/plerixafor-for-autologous-stem-cell-mobilization-and-transplantation-for-patients-in-ontario
#17
C T Kouroukis, N P Varela, C Bredeson, J Kuruvilla, A Xenocostas
BACKGROUND: High-dose chemotherapy with autologous stem-cell transplantation (asct) is an accepted part of standard therapy for patients with hematologic malignancies. Usually, stem-cell mobilization uses granulocyte colony-stimulating factor (g-csf); however, some patients are not able to be mobilized with chemotherapy and g-csf, and such patients could be at higher risk of failing mobilization. Plerixafor is a novel mobilization agent that is absorbed quickly after subcutaneous injection and, at the recommended dose of 0...
August 2016: Current Oncology
https://www.readbyqxmd.com/read/27535663/plerixafor-a-cxcr4-antagonist-following-myeloablative-allogeneic-hematopoietic-stem-cell-transplantation-enhances-hematopoietic-recovery
#18
Michael M B Green, Nelson Chao, Saurabh Chhabra, Kelly Corbet, Cristina Gasparetto, Ari Horwitz, Zhiguo Li, Jagadish Kummetha Venkata, Gwynn Long, Alice Mims, David Rizzieri, Stefanie Sarantopoulos, Robert Stuart, Anthony D Sung, Keith M Sullivan, Luciano Costa, Mitchell Horwitz, Yubin Kang
BACKGROUND: The binding of CXCR4 with its ligand (stromal-derived factor-1) maintains hematopoietic stem/progenitor cells (HSPCs) in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT) promotes hematopoiesis by inducing HSC proliferation. METHODS: We conducted a phase I/II trial of plerixafor on hematopoietic cell recovery following myeloablative allogeneic HSCT. Patients with hematologic malignancies receiving myeloablative conditioning were enrolled...
August 17, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27519279/selective-depletion-of-%C3%AE-%C3%AE-t-cells-and-b-cells-for-human-leukocyte-antigen-haploidentical-hematopoietic-stem-cell-transplantation-a-three-year-follow-up-of-procedure-efficiency
#19
Giuseppina Li Pira, David Malaspina, Elia Girolami, Simone Biagini, Elisabetta Cicchetti, Gianpiero Conflitti, Manuel Broglia, Stefano Ceccarelli, Stefania Lazzaro, Daria Pagliara, Antonella Meschini, Alice Bertaina, Mauro Montanari, Franco Locatelli
HLA-haploidentical family donors represent a valuable option for children requiring allogeneic hematopoietic stem cell transplantation (HSCT). Because graft-versus-host diseases (GVHD) is a major complication of HLA-haploidentical HSCT because of alloreactive T cells in the graft, different methods have been used for ex vivo T cell depletion. Removal of donor αβ T cells, the subset responsible for GVHD, and of B cells, responsible for post-transplantation lymphoproliferative disorders, have been recently developed for HLA-haploidentical HSCT...
November 2016: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/27496214/quantitation-of-human-cells-that-produce-neutrophils-and-platelets-in-vivo-obtained-from-normal-donors-treated-with-granulocyte-colony-stimulating-factor-and-or-plerixafor
#20
Paul H Miller, Naoto Nakamichi, David J H F Knapp, Gabrielle Rabu, Kirk R Schultz, David M Jones, Stephen Couban, Connie J Eaves
Plerixafor (P) together with granulocyte colony-stimulating factor (G) is now recognized as an important strategy for mobilizing hematopoietic cells for use in patients given myelosuppressive therapies. However, quantitative comparisons of their ability to mobilize human cells with different hematopoietic activities in vitro or in vivo (in immunodeficient mice) and their interrelationships have not been investigated. To address these questions, we collected samples from 5 normal adult volunteers before and after administering P alone and from another 5 before and after a 4-day course of G and again after a subsequent injection of P...
November 2016: Biology of Blood and Marrow Transplantation
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