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Plerixafor

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https://www.readbyqxmd.com/read/28303154/mesenchymal-stem-cell-administration-in-patients-with-chronic-obstructive-pulmonary-disease-state-of-the-science
#1
REVIEW
Shih-Lung Cheng, Ching-Hsiung Lin, Chao-Ling Yao
Patients with chronic obstructive pulmonary disease (COPD) have chronic, irreversible airway inflammation; currently, there is no effective or curative treatment and the main goals of COPD management are to mitigate symptoms and improve patients' quality of life. Stem cell based therapy offers a promising therapeutic approach that has shown potential in diverse degenerative lung diseases. Preclinical studies have demonstrated encouraging outcomes of mesenchymal stem/stromal cells (MSCs) therapy for lung disorders including emphysema, bronchopulmonary dysplasia, fibrosis, and acute respiratory distress syndrome...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28292947/mobilization-of-allogeneic-peripheral-blood-stem-cell-donors-with-intravenous-plerixafor-mobilizes-a-unique-graft
#2
Mark A Schroeder, Michael P Rettig, Sandra Lopez, Stephanie Christ, Mark Fiala, William Eades, Fazia A Mir, Jin Shao, Kyle McFarland, Kathryn Trinkaus, William Shannon, Elena Deych, Jinsheng Yu, Ravi Vij, Keith Stockerl-Goldstein, Amanda F Cashen, Geoffery L Uy, Camille N Abboud, Peter Westervelt, John F DiPersio
A single subcutaneous (SC) injection of plerixafor results in rapid mobilization of hematopoietic progenitors but fails to mobilize 33% of normal allogeneic sibling donors in one apheresis. We hypothesized that changing the route of administration of plerixafor from SC to intravenous (IV) may overcome the low stem cell yields and allow collection in one day. A phase I trial followed by a phase II efficacy trial was conducted in allogeneic sibling donors. The optimal dose of IV plerixafor was determined to be 0...
March 14, 2017: Blood
https://www.readbyqxmd.com/read/28286619/optimizing-stem-cells-mobilization-strategies-to-ameliorate-patient-outcomes-a-review-of-guide-lines-and-recommendations
#3
REVIEW
Saeed Mohammadi, Ashraf Malek Mohammadi, Mohsen Nikbakht, Amir Hossein Norooznezhad, Kamran Alimoghaddam, Ardeshir Ghavamzadeh
Peripheral blood stem cell transplantation (PBSCT) is an effective treatment for hematological malignancies. Mobilization of peripheral blood progenitor cells performs in different ways among transplantation centers. Forceful mobilization schedules are comprised of growth factor alone, chemotherapy along with growth factor and also, a newly combination of novel agent such as plerixafor with any approach. With the appearance of numerous modifications in stem cell mobilization field over the past decade and advent of novel stem cell mobilization techniques, it seems to be necessary to review recent publications about stem cell mobilization strategies to respond above cited issues...
January 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28282031/a-phase-1-2-study-of-chemosensitization-with-plerixafor-plus-g-csf-in-relapsed-or-refractory-acute-myeloid-leukemia
#4
G L Uy, M P Rettig, R M Stone, M Y Konopleva, M Andreeff, K McFarland, W Shannon, T R Fletcher, T Reineck, W Eades, K Stockerl-Goldstein, C N Abboud, M A Jacoby, P Westervelt, J F DiPersio
No abstract text is available yet for this article.
March 10, 2017: Blood Cancer Journal
https://www.readbyqxmd.com/read/28274958/cabozantinib-eradicates-advanced-murine-prostate-cancer-by-activating-anti-tumor-innate-immunity
#5
Akash Patnaik, Kenneth D Swanson, Eva Csizmadia, Aniruddh Solanki, Natalie Landon-Brace, Marina P Gehring, Katja Helenius, Brian M Olson, Athalia R Pyzer, Lily C Wang, Olivier Elemento, Jesse Novak, Thomas B Thornley, John M Asara, Laleh Montaser, Joshua J Timmons, Todd M Morgan, Yugang Wang, Elena Levantini, John G Clohessy, Kathleen Kelly, Pier Paolo Pandolfi, Jacalyn M Rosenblatt, David E Avigan, Huihui Ye, Jeffrey M Karp, Sabina Signoretti, Steven P Balk, Lewis C Cantley
Several kinase inhibitors that target aberrant signaling pathways in tumor cells have been deployed in cancer therapy. However, their impact on the tumor immune microenvironment remains poorly understood. The tyrosine kinase inhibitor cabozantinib showed striking responses in cancer clinical trial patients across several malignancies. Here we show that cabozantinib rapidly eradicates invasive, poorly-differentiated PTEN/p53 deficient murine prostate cancer. This was associated with enhanced release of neutrophil chemotactic factors from tumor cells, including CXCL12 and HMGB1, resulting in robust infiltration of neutrophils into the tumor...
March 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28067870/a-single-center-s-experience-using-four-different-front-line-mobilization-strategies-in-lymphoma-patients-planned-to-undergo-autologous-hematopoietic-cell-transplantation
#6
B M Haverkos, Y Huang, P Elder, L O'Donnell, D Scholl, B Whittaker, S Vasu, S Penza, L A Andritsos, S M Devine, S M Jaglowski
In an otherwise eligible patient with relapsed lymphoma, inadequate mobilization of hematopoietic stem cells (HSCs) is a limiting factor to proceeding with an autologous hematopoietic cell transplantation (auto-HCT). Multiple strategies have been used to mobilize an adequate number of HSCs with no obvious front-line strategy. We report a single institutional experience mobilizing HSCs using four different approaches in lymphoma patients. We prospectively collected mobilization outcomes on patients planned to undergo auto-HCT at Ohio State University...
January 9, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28040478/cathepsin-k-cleavage-of-sdf-1%C3%AE-inhibits-its-chemotactic-activity-towards-glioblastoma-stem-like-cells
#7
Vashendriya V V Hira, Urška Verbovšek, Barbara Breznik, Matic Srdič, Marko Novinec, Hala Kakar, Jill Wormer, Britt Van der Swaan, Brigita Lenarčič, Luiz Juliano, Shwetal Mehta, Cornelis J F Van Noorden, Tamara T Lah
Glioblastoma (GBM) is the most aggressive primary brain tumor with poor patient survival that is at least partly caused by malignant and therapy-resistant glioma stem-like cells (GSLCs) that are protected in GSLC niches. Previously, we have shown that the chemo-attractant stromal-derived factor-1α (SDF-1α), its C-X-C receptor type 4 (CXCR4) and the cysteine protease cathepsin K (CatK) are localized in GSLC niches in glioblastoma. Here, we investigated whether SDF-1α is a niche factor that through its interactions with CXCR4 and/or its second receptor CXCR7 on GSLCs facilitates their homing to niches...
December 28, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28034992/plerixafor-and-g-csf-combination-mobilizes-hematopoietic-stem-and-progenitors-cells-with-a-distinct-transcriptional-profile-and-a-reduced-in-vivo-homing-capacity-compared-to-plerixafor-alone
#8
Maria Rosa Lidonnici, Annamaria Aprile, Marta Claudia Frittoli, Giacomo Mandelli, Ylenia Paleari, Antonello Spinelli, Bernhard Gentner, Matilde Zambelli, Cristina Parisi, Laura Bellio, Elena Cassinerio, Laura Zanaboni, Maria Domenica Cappellini, Fabio Ciceri, Sarah Marktel, Giuliana Ferrari
No abstract text is available yet for this article.
December 29, 2016: Haematologica
https://www.readbyqxmd.com/read/28034547/how-to-manage-poor-mobilizers-for-high-dose-chemotherapy-and-autologous-stem-cell-transplantation
#9
REVIEW
Pinar Ataca Atilla, Sule Mine Bakanay Ozturk, Taner Demirer
Today, peripheral blood stem cells are the preferred source of stem cells over bone marrow. Therefore, mobilization plays a crutial role in successful autologous stem cell transplantation. Poor mobilization is generally defined as failure to achieve the target level of at least 2×10(6) CD34(+) cells/kg body weight. There are several strategies to overcome poor mobilization: 1) Larger volume Leukapheresis (LVL) 2) Re-mobilization 3) Plerixafor 4) CM+Plerixafor (P)+G-CSF and 5) Bone Marrow Harvest. In this review, the definitions of successful and poor mobilization are discussed...
December 26, 2016: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/27987208/poor-stem-cell-harvest-may-not-always-be-related-to-poor-mobilization-lessons-gained-from-a-mobilization-study-in-patients-with-%C3%AE-thalassemia-major
#10
Varnavas C Constantinou, Asimina Bouinta, Garyfalia Karponi, Fani Zervou, Penelope-Georgia Papayanni, George Stamatoyannopoulos, Achilles Anagnostopoulos, Evangelia Yannaki
BACKGROUND: Hematopoietic stem cell mobilization and leukapheresis in adult patients with β-thalassemia have recently been optimized in the context of clinical trials for obtaining hematopoietic stem cells for thalassemia gene therapy. In some patients, however, the yield of cluster of differentiation 34-positive (CD34+) cells was poor despite successful mobilization, and a modification of apheresis settings was mandatory for harvest rescue. STUDY DESIGN AND METHODS: Data were analyzed from 20 adult patients with β-thalassemia who were enrolled in a clinical trial of optimizing mobilization strategies for stem cell gene therapy...
December 17, 2016: Transfusion
https://www.readbyqxmd.com/read/27982313/hodgkin-s-lymphoma-evaluation-of-patients-submitted-to-autologous-transplantation-of-hematopoietic-cells-in-the-hematology-service-of-the-hospital-walter-cant%C3%A3-dio-fortaleza-brazil
#11
Fernando Barroso Duarte, Mabel Gomes de Brito Fernandes, Jacques Kaufmann, Karine Sampaio Nunes Barroso, João Paulo de Vasconcelos Leitão, Beatriz Stela Gomes de Souza Pitombeira Araujo, Clara Maria Bastos Eloy da Costa, Acy Teles Quixadá-Medica, Jacqueline de Souza Holanda, Samuel Vasconcelos Landim, Maria Helena Pitombeira
The Autologous HSCT is an important alternative for refractory or recurrent HL patients in terms of survival and improved quality of life. This study analyzes the results of autologous BMT performed in HL patients in the Transplant Unit of the HUWC/ HEMOCE (Fortaleza - CE, Brazil). Fifty-two transplanted patients were studied from January 2009 to October 2015, among them, 30 men and 22 women, mean age of 28.2 years. All of them received GCS-F during the mobilization, in some cases associated with Vinorelbine or Plerixafor, with CD34 collection averaging 4...
October 2016: Revista da Associação Médica Brasileira
https://www.readbyqxmd.com/read/27965305/bone-marrow-cell-trafficking-analyzed-by-89zr-oxine-positron-emission-tomography-in-a-murine-transplantation-model
#12
Kingsley O Asiedu, Sho Koyasu, Lawrence P Szajek, Peter L Choyke, Noriko Sato
PURPOSE: The success of hematopoietic stem cell transplantation (HSCT) depends on donor cell homing to the bone marrow (BM). However, there is no reliable method of noninvasively monitoring the kinetics and distribution of transferred cells. Using Zirconium-89 ((89)Zr)-oxine cell labeling combined with positron emission tomography (PET) imaging, we sought to visualize and quantify donor cell homing in a mouse BM transplantation model. EXPERIMENTAL DESIGN: The effect of (89)Zr-oxine labeling on BM cell viability and differentiation was evaluated in vitro...
December 13, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#13
Christine Oswald, Mathieu Rappas, James Kean, Andrew S Doré, James C Errey, Kirstie Bennett, Francesca Deflorian, John A Christopher, Ali Jazayeri, Jonathan S Mason, Miles Congreve, Robert M Cooke, Fiona H Marshall
Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells. They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases. Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27905003/new-agents-in-hsc-mobilization
#14
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
#15
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
#16
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...
January 2017: 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
#17
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
#18
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
#19
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
#20
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...
February 2017: Anti-cancer Drugs
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