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Plerixafor

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https://www.readbyqxmd.com/read/29140182/tgf-%C3%AE-1-and-cxcl12-modulate-proliferation-and-chemotherapy-sensitivity-of-acute-myeloid-leukemia-cells-co-cultured-with-multipotent-mesenchymal-stromal-cells
#1
Roland Christian Schelker, Sabine Iberl, Gunnar Müller, Christina Hart, Wolfgang Herr, Jochen Grassinger
OBJECTIVES: Multipotent mesenchymal stromal cells (MSCs) play a central role within the bone marrow (BM) niche, supporting hematopoiesis via soluble factors like cytokines and chemokines. In our study, we sought to investigate the effect of blocking transforming growth factor beta 1 (TGF-β1) and C-X-C motif chemokine 12 (CXCL12) receptor CXCR4 on acute myeloid leukemia (AML) cells in an MSC co-culture system. METHODS: Human MSCs were obtained by BM aspirates and their phenotype and functional properties were confirmed in vitro...
November 15, 2017: Hematology (Amsterdam, Netherlands)
https://www.readbyqxmd.com/read/29134662/dose-capping-of-plerixafor-in-patients-weighing%C3%A2-more-than-100%C3%A2-kg-at-one-vial-led-to-successful-mobilization-outcomes-and-significant-cost-savings
#2
Gabriel Park, Sepideh Shayani, Tracey Stiller, Shirong Wang, Shan Yuan
BACKGROUND: Plerixafor is frequently used as an adjunct agent to improve mobilization of peripheral blood stem cells in many clinical settings. However, its high cost (>$8000 per single-use 24-mg vial) is a significant concern. The manufacturer-recommended dose is 0.24 mg/kg. Therefore, patients weighing more than 100 kg would require a second vial, thus doubling the drug cost per dose. We implemented a policy of capping the dose of plerixafor at 24 mg, or one vial, for patients weighing more than 100 kg...
November 13, 2017: Transfusion
https://www.readbyqxmd.com/read/29132746/diabetes-mellitus-as-a-poor-mobilizer-condition
#3
REVIEW
Gian Paolo Fadini, John F DiPersio
Hematopoietic stem cell (HSC) transplantation in an effective and curative therapy for numerous hematological malignancies. Mobilization of HSCs from bone marrow (BM) to peripheral blood (PB) followed by apheresis is the gold standard for obtaining HSCs for both autologous and allogeneic stem cell transplantation. After administration of granulocyte-colony stimulating factor (G-CSF), up to 30% of patients fail to mobilize "optimal" numbers of HSCs required for engraftment. This review summarizes the current experimental and clinical evidence that diabetes mellitus is a risk factor for poor mobilization...
November 8, 2017: Blood Reviews
https://www.readbyqxmd.com/read/29125295/structure-activity-relationships-and-biological-characterization-of-a-novel-potent-and-serum-stable-c-x-c-chemokine-receptor-type-4-cxcr4-antagonist
#4
Salvatore Di Maro, Francesco Saverio Di Leva, Anna Maria Trotta, Diego Brancaccio, Luigi Portella, Michela Aurilio, Stefano Tomassi, Anna Messere, Deborah Sementa, Secondo Lastoria, Alfonso Carotenuto, Ettore Novellino, Stefania Scala, Luciana Marinelli
In our ongoing pursuit of CXCR4 antagonists as potential anticancer agents, we recently developed a potent, selective and plasma stable peptide, Ac-Arg-Ala-[D-Cys-Arg-Phe-Phe-Cys]-COOH (3). Nevertheless, this compound was still not enough potent (IC50 ≈ 53 nM) to enter preclinical studies. Thus, a lead-optimization campaign was here undertaken to further improve the binding affinity of 3 while preserving its selectivity and proteolytic stability. Specifically, extensive structure-activity relationships (SARs) investigations were carried out on both its aromatic and disulfide forming amino acids...
November 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29081261/stem-cell-mobilization-in-poor-mobilizers-with-multiple-myeloma-or-lymphoma-before-and-after-introduction-of-plerixafor-a-single-center-comparative-analysis-using-a-cost-efficient-single-fixed-dose-schedule
#5
Christine Greil, Gabriele Ihorst, Chrissoula Kiote-Schmidt, Steffi Hildenbeutel, Katja Kühbach, Roland Bosse, Justus Duyster, Monika Engelhardt, Ralph Wäsch
No abstract text is available yet for this article.
October 30, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29075055/single-dose-preemptive-plerixafor-for-stem-cell-mobilization-for-asct-after-lenalidomide-based-therapy-in-multiple-myeloma-impact-in-resource-limited-setting
#6
Rajiv Kumar, Rajan Kapoor, Bhushan Asthana, Jasjit Singh, Tarun Verma, Rajesh Chilaka, N K Singh, Ajay Sharma, S Das, Velu Nair
Peripheral blood stem cell mobilization with cytokines for autologous stem cell transplant in multiple myeloma is adversely affected by initial induction therapy consisting of either Lenalidomide or cytotoxic drugs, with failure rates of up to 45%. The use of Plerixafor with G-CSF for PBSC mobilisation significantly improves the chances of a successful mobilization. Plerixafor is a costly therapy and increases the overall costs of ASCT which can affect the number of patients being taken up for ASCT in resource limited settings...
December 2017: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/29066537/how-i-treat-warts-hypogammaglobulinemia-infections-and-myelokathexis-whim-syndrome
#7
Raffaele Badolato, Jean Donadieu
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome is a genetic disease characterized by neutropenia, lymphopenia, susceptibility to infections, and myelokathexis, which describes degenerative changes of mature neutrophils and hyperplasia of bone marrow myeloid cells. Some patients present with hypogammaglobulinemia and/or refractory warts of skin and genitalia. Congenital cardiac defects constitute uncommon manifestations of the disease. The disorder, which is inherited as an autosomal dominant trait, is caused by heterozygous mutations of the chemokine receptor CXCR4...
October 24, 2017: Blood
https://www.readbyqxmd.com/read/29058701/nsaid-treatment-with-meloxicam-enhances-peripheral-stem-cell-mobilization-in-myeloma
#8
B Jeker, U Novak, B Mansouri Taleghani, G M Baerlocher, K Seipel, B U Mueller, M Bigler, D Betticher, J-M Luethi, S Farese, A Ruefer, T Pabst
Chemotherapy with G-CSF is used to mobilize peripheral stem cells in multiple myeloma (MM) patients, with plerixafor as a rescue strategy for poorly mobilizing patients. Preclinical studies suggested that the nonsteroidal anti-inflammatory drug meloxicam enhances the mobilization of CD34(+) cells. In this single-center study, we evaluated whether adding meloxicam to chemotherapy/G-CSF mobilization increases peripheral hematopoietic CD34(+) cell levels and reduces the need of using plerixafor. We prospectively compared two consecutive cohorts of MM patients in first remission mobilized with G-CSF and non-myelosuppressive chemotherapy with vinorelbine or gemcitabine...
October 23, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29057173/pathogenesis-diagnosis-and-therapeutic-strategies-in-whim-syndrome-immunodeficiency
#9
Lauren E Heusinkveld, Erin Yim, Alexander Yang, Ari B Azani, Qian Liu, Ji-Liang Gao, David H McDermott, Philip M Murphy
21 INTRODUCTION: WHIM syndrome is a rare combined primary immunodeficiency disorder caused by autosomal dominant gain-of-function mutations in the chemokine receptor CXCR4. It is the only Mendelian condition known to be caused by mutation of a chemokine or chemokine receptor. As such, it provides a scientific opportunity to understand chemokine-dependent immunoregulation in humans and a medical opportunity to develop mechanism-based treatment and cure strategies. 22 AREAS COVERED: This review covers the clinical features, genetics, immunopathogenesis and clinical management of WHIM syndrome...
2017: Expert Opinion on Orphan Drugs
https://www.readbyqxmd.com/read/28916148/chemokine-receptor-directed-imaging-and-therapy
#10
REVIEW
Andreas K Buck, Antje Stolzenburg, Heribert Hänscheid, Andreas Schirbel, Katharina Lückerath, Margret Schottelius, Hans-Jürgen Wester, Constantin Lapa
The C-X-C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. The CXCR4/CXCL12 interplay can be disrupted by CXCR4 antagonists such as Plerixafor which are already in daily clinical use, i.e. for mobilization and subsequent harvesting of hematopoietic progenitor cells and stem cell transplantation. In a pathological condition, involvement in the process of metastasis and homing of cancer cells to a protective niche has been described, making CXCR4 an attractive target for imaging and treatment of malignant diseases...
November 1, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28894310/chemical-stability-of-plerixafor-after-opening-of-single-use-vial
#11
Jack T Seki, Andrea Bozovic, Roy Lee, Rita Kwong, Eshetu G Atenafu, Anna Xu, Jin-Hyeun Huh
BACKGROUND: The addition of the immunostimulant plerixafor to the current standard-of-care regimens of granulocyte colony-stimulating growth factor with or without chemotherapy has improved clinical results in terms of successful stem cell mobilization and the outcomes of stem cell transplant in various settings. With this medical innovation has come an added financial cost for institutions where stem cell transplants are routinely performed, and there may be a further financial burden when the contents of partial vials of the drug are wasted, given that plerixafor vials (Mozobil, Sanofi-Aventis Canada Inc) are currently deemed suitable only for single use...
July 2017: Canadian Journal of Hospital Pharmacy
https://www.readbyqxmd.com/read/28879595/preemptive-plerixafor-injection-added-to-pegfilgrastim-after-chemotherapy-in-non-hodgkin-lymphoma-patients-mobilizing-poorly
#12
A Partanen, J Valtola, A Ropponen, K Vasala, K Penttilä, L Ågren, M Pyörälä, T Nousiainen, T Selander, P Mäntymaa, J Pelkonen, V Varmavuo, E Jantunen
Filgrastim is usually combined with chemotherapy to mobilize hematopoietic progenitor cells in non-Hodgkin lymphoma (NHL) patients. Limited information is available on the efficacy of a preemptive plerixafor (PLER) injection in poor mobilizers after chemotherapy and pegfilgrastim. In this prospective study, 72 patients with NHL received chemotherapy plus pegfilgrastim, and 25 hard-to-mobilize patients received also PLER. The usefulness and efficacy of our previously developed algorithm for PLER use in pegfilgrastim-containing mobilization regimen were evaluated as well as the graft cellular composition, hematological recovery, and outcome after autologous stem cell transplantation (auto-SCT) according to the PLER use...
November 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28817386/cxcr4-blockade-with-amd3100-enhances-taxol-chemotherapy-to-limit-ovarian-cancer-cell-growth
#13
Patrick M Reeves, Mojgan A Abbaslou, Farah R W Kools, Mark C Poznansky
The standard of care for ovarian cancer includes initial treatment with chemotherapy. Despite initial efficacy, over 70% of patients develop recurrence; thus, there is a need to identify novel approaches that can improve therapeutic outcomes. We evaluated AMD3100 (Plerixafor), an FDA-approved CXCR4 inhibitor, as a potential adjunctive therapy for low-dose Taxol (Paclitaxel) by assessing the impact on in-vitro ovarian cancer cell proliferation. Proliferation was a measure for both human TOV-112D and murine ID8 ovarian cancer cells incubated with AMD3100 and Taxol, either individually or in combination...
August 16, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28801449/engraftment-and-in-vivo-proliferation-advantage-of-gene-corrected-mobilized-cd34-cells-from-fanconi-anemia-patients
#14
Paula Río, Susana Navarro, Guillermo Guenechea, Rebeca Sánchez-Domínguez, Maria Luisa Lamana, Rosa Yañez, Jose A Casado, Parinda A Mehta, Maria Roser Pujol, Jordi Surrallés, Sabine Charrier, Anne Galy, José C Segovia, Cristina Díaz de Heredia, Julián Sevilla, Juan A Bueren
Previous Fanconi anemia (FA) gene therapy studies have failed to demonstrate engraftment of gene-corrected hematopoietic stem and progenitor cells (HSPCs) from FA patients, either after autologous transplantation or infusion into immunodeficient mice. In this study, we demonstrate that a validated short transduction protocol of G-CSF plus plerixafor-mobilized CD34(+) cells from FA-A patients with a therapeutic FANCA-lentiviral vector corrects the phenotype of in vitro cultured hematopoietic progenitor cells...
September 28, 2017: Blood
https://www.readbyqxmd.com/read/28797783/results-of-a-prospective-randomized-open-label-noninferiority-study-of-tbo-filgrastim-granix-versus-filgrastim-neupogen-in-combination-with-plerixafor-for-autologous-stem-cell-mobilization-in-patients-with-multiple-myeloma-and-non-hodgkin-lymphoma
#15
Pavan Kumar Bhamidipati, Mark A Fiala, Brenda J Grossman, John F DiPersio, Keith Stockerl-Goldstein, Feng Gao, Geoffrey L Uy, Peter Westervelt, Mark A Schroeder, Amanda F Cashen, Camille N Abboud, Ravi Vij
Autologous hematopoietic stem cell transplantation (auto-HSCT) improves survival in patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL). Traditionally, filgrastim (Neupogen; recombinant G-CSF) has been used in as a single agent or in combination with plerixafor for stem cell mobilization for auto-HSCT. In Europe, a biosimilar recombinant G-CSF (Tevagrastim) has been approved for various indications similar to those of reference filgrastim, including stem cell mobilization for auto-HSCT; however, in the United States, tbo-filgrastim (Granix) is registered under the original biological application and is not approved for stem cell mobilization...
August 7, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28783870/cxcr4-antagonist-delivery-on-decellularized-skin-scaffold-facilitates-impaired-wound-healing-in-diabetic-mice-by-increasing-expression-of-sdf-1-and-enhancing-migration-of-cxcr4-positive-cells
#16
Hao Liu, Hanping Liu, Xiaoyuan Deng, Maosheng Chen, Xue Han, Wenxia Yan, Ning Wang
C-X-C chemokine receptor type 4 (CXCR4) is an alpha-chemokine receptor specific for stromal cell-derived factor 1 (SDF-1 also called CXCL12). The antagonist of CXCR4 can mobilize CD34+ cells and hematopoietic stem cells from bone marrow within several hours, and it has an efficacy on diabetes ulcer through acting on the SDF-1/CXCR4 axis. In this study, we investigated for the first time whether the antagonist of CXCR4 (Plerixafor/AMD3100) delivered on acellular dermal matrix (ADM) may accelerate diabetes-impaired wound healing...
June 8, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28768055/harnessing-cxcr4-antagonists-in-stem-cell-mobilization-hiv-infection-ischemic-diseases-and-oncology
#17
REVIEW
Lun Kelvin Tsou, Ying-Huey Huang, Jen-Shin Song, Yi-Yu Ke, Jing-Kai Huang, Kak-Shan Shia
CXCR4 antagonists (e.g., Plerixafor(TM) ) have been successfully validated as stem cell mobilizers for peripheral blood stem cell transplantation. Applications of the CXCR4 antagonists have heralded the era of cell-based therapy and opened a potential therapeutic horizon for many unmet medical needs such as kidney injury, ischemic stroke, cancer, and myocardial infarction. In this review, we first introduce the central role of CXCR4 in diverse cellular signaling pathways and discuss its involvement in several disease progressions...
August 2, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28718760/cd25-expression-and-outcomes-in-older-patients-with-acute-myelogenous-leukemia-treated-with-plerixafor-and-decitabine
#18
John N Allan, Gail J Roboz, Gulce Askin, Ellen Ritchie, Joseph Scandura, Paul Christos, Duane C Hassane, Monica L Guzman
We investigated CD25 expression in older (≥60 years) patients with new acute myelogenous leukemia treated with decitabine and plerixafor. Patients resistant to therapy or survival ≤1 year had significantly higher percentages of CD25(pos) myeloid blasts in baseline bone marrow. CD25(pos) patients had an increased odds of resistance compared to CD25(neg) patients (p = .015). In univariate analysis, we found CD25(pos) patients had inferior survival compared to CD25(neg) (p = .002). In patients with intermediate risk cytogenetics, CD25(pos) status stratified patients associating with inferior survival (p = ...
July 18, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28675459/stimulation-of-adrenergic-activity-by-desipramine-enhances-hematopoietic-stem-and-progenitor-cell-mobilization-along-with-g-csf-in-multiple-myeloma-a-pilot-study
#19
Aditi Shastri, Anjali Budhathoki, Stefan K Barta, Noah Kornblum, Olga Derman, Ramakrishna Battini, Radha Raghupathy, Amit K Verma, Paul S Frenette, Ira Braunschweig, Murali Janakiram
Hematopoietic stem cell (HSC) release is positively regulated by the sympathetic nervous system through the β3 adrenergic receptor. Preclinical studies have demonstrated that the combination of desipramine and G-CSF resulted in improved HSC mobilization. Here, we present the results of an open-label single-arm pilot study in patients with multiple myeloma undergoing autologous stem cell transplantation (ASCT) to assess the safety and efficacy of desipramine combined with G-SCF to induce HSC mobilization. The primary endpoint was safety of the combination including engraftment kinetics...
October 2017: American Journal of Hematology
https://www.readbyqxmd.com/read/28670693/cxcl12-and-cxcr7-are-relevant-targets-to-reverse-cell-adhesion-mediated-drug-resistance-in-multiple-myeloma
#20
Johannes M Waldschmidt, Anna Simon, Dagmar Wider, Stefan J Müller, Marie Follo, Gabriele Ihorst, Sarah Decker, Joschka Lorenz, Manik Chatterjee, Abdel K Azab, Justus Duyster, Ralph Wäsch, Monika Engelhardt
Cell adhesion-mediated drug resistance (CAM-DR) by the bone marrow (BM) is fundamental to multiple myeloma (MM) propagation and survival. Targeting BM protection to increase the efficacy of current anti-myeloma treatment has not been extensively pursued. To extend the understanding of CAM-DR, we hypothesized that the cytotoxic effects of novel anti-myeloma agents may be abrogated by the presence of BM stroma cells (BMSCs) and restored by addition of the CXCL12 antagonist NOX-A12 or the CXCR4 inhibitor plerixafor...
October 2017: British Journal of Haematology
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