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https://www.readbyqxmd.com/read/28916148/chemokine-receptor-directed-imaging-and-therapy
#1
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...
September 12, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28894310/chemical-stability-of-plerixafor-after-opening-of-single-use-vial
#2
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
#3
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...
September 7, 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28817386/cxcr4-blockade-with-amd3100-enhances-taxol-chemotherapy-to-limit-ovarian-cancer-cell-growth
#4
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
#5
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 Bueren
Previous Fanconi anemia (FA) gene therapy studies have failed to demonstrate engraftment of gene corrected hematopoietic stem and progenitor cells (HSPC) 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. Transplantation of transduced FA CD34(+) cells into immunodeficient mice resulted in reproducible engraftment of myeloid, lymphoid and CD34(+) cells...
August 11, 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
#6
Pavan Kumar Bhamidipati, Mark A Fiala, Brenda J Grossman, John F DiPersio, Keith Stokerl-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
#7
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
#8
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
#9
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
#10
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...
July 4, 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
#11
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...
July 2, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28638088/chemokine-receptor-cxcr4-regulates-camkii-creb-pathway-in-spinal-neurons-that-underlies-cancer-induced-bone-pain
#12
Xue-Ming Hu, Hui Zhang, Heng Xu, Hai-Long Zhang, Li-Ping Chen, Wen-Qiang Cui, Wei Yang, Wen Shen
We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. We used a tumor cell implantation (TCI) model and observed that CXCR4, p-CaMKII and p-CREB were persistently up-regulated in spinal neurons. CXCR4 also co-expressed with p-CaMKII and p-CREB, and mediated p-CaMKII and p-CREB expression after TCI...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28631842/uk-consensus-statement-on-the-use-of-plerixafor-to-facilitate-autologous-peripheral-blood-stem-cell-collection-to-support-high-dose-chemoradiotherapy-for-patients-with-malignancy
#13
Kenneth W Douglas, Maria Gilleece, Patrick Hayden, Hannah Hunter, Peter R E Johnson, Charlotte Kallmeyer, Ram K Malladi, Shankara Paneesha, Rachel Pawson, Michael Quinn, Kavita Raj, Deborah Richardson, Stephen Robinson, Nigel Russell, John Snowden, Anna Sureda, Eleni Tholouli, Kirsty Thomson, Mike Watts, Keith M Wilson
Plerixafor is a CXC chemokine receptor (CXCR4) antagonist that mobilizes stem cells in the peripheral blood. It is indicated (in combination with granulocyte-colony stimulating factor [G-CSF]) to enhance the harvest of adequate quantities of cluster differentiation (CD) 34+ cells for autologous transplantation in patients with lymphoma or multiple myeloma whose cells mobilize poorly. Strategies for use include delayed re-mobilization after a failed mobilization attempt with G-CSF, and rescue or pre-emptive mobilization in patients in whom mobilization with G-CSF is likely to fail...
June 20, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28581475/the-choice-of-in-hospital-or-home-administration-for-plerixafor-injection-to-poor-mobilizers-has-no-adverse-consequence-on-subsequent-hematopoietic-stem-cell-harvest
#14
C Chabannon, F Bijou, J-M Grouin, P Drillat, N Milpied, M Mohty
No abstract text is available yet for this article.
August 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28580637/influence-of-plerixafor-on-the-mobilization-of-cd34-cell-subpopulations-and-lymphocyte-subtypes
#15
Nina Worel, Nelli Frank, Christian Frech, Gerhard Fritsch
BACKGROUND: Peripheral blood stem cells mobilized with granulocyte-colony-stimulating factor (G-CSF) with or without chemotherapy are routinely used for autologous hematopoietic cell transplantation. Plerixafor, a chemokine-receptor inhibitor, increases the amount of circulating CD34+ cells and improves harvest results. However, limited information is available regarding the composition of apheresis products with respect to CD34+ and lymphocyte subtypes collected after various mobilization regimens...
June 5, 2017: Transfusion
https://www.readbyqxmd.com/read/28573902/cost-effectiveness-of-on-demand-plerixafor-added-to-chemotherapy-and-granulocyte-colony-stimulating-factor-for-peripheral-blood-stem-cell-mobilization-in-multiple-myeloma
#16
Giuseppe Milone, Massimo Martino, Salvatore Leotta, Andrea Spadaro, Valentina Zammit, Alessandra Cupri, Giuseppe Avola, Maria Grazia Camuglia, Annalia Di Marco, Potito Scalzulli, Mara Morelli, Attilio Olivieri, Giovanni Tripepi
We here report final results of a phase II/III prospective study that evaluated in Multiple Myeloma the use of on-demand plerixafor (PLX) added to mobilizing chemotherapy for patients showing predictive signs of mobilization failure. A total of 111 patients with MM were registered, all received cyclophosphamide 4 g/m(2) and granulocyte colony-stimulating factor (G-CSF). Overall, a successful CD34+ cell mobilization was achieved in 97.2% (108/111) of patients. Minimum harvest (≥2.0 × 10(6) CD34+ cells/kg) was achieved in 97...
June 2, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28556233/poor-peripheral-blood-stem-cell-mobilization-affects-long-term-outcomes-in-multiple-myeloma-patients-undergoing-autologous-stem-cell-transplantation
#17
Jan S Moreb, Michael Byrne, Ilicia Shugarman, Fei Zou, Sican Xiong, William S May, Maxim Norkin, John Hiemenz, Randall Brown, Christopher Cogle, John R Wingard, Jack W Hsu
BACKGROUND: Peripheral blood stem cell (PBSC) mobilization is routinely undertaken prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). A number of studies have identified risk factors for poor PBSC mobilization, however, little data exists to correlate mobilization with disease-specific outcomes in this patient population. Prospective work in MM has demonstrated similar outcomes in a homogenous patient population. METHODS: In this single institution analysis, we retrospectively studied the impact of poor PBSC mobilization on progression free survival (PFS) and OS in MM patients undergoing PBSC mobilization...
May 29, 2017: Journal of Clinical Apheresis
https://www.readbyqxmd.com/read/28530669/addition-of-plerixafor-to-g-csf-is-useful-to-achieve-efficient-collection-even-in-very-poor-mobilizers-hope-for-patients-with-diminished-hematopoietic-function
#18
M Mohty, P Drillat, J-M Grouin, F Bijou, N Milpied, C Chabannon
No abstract text is available yet for this article.
May 22, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28527129/efficacy-and-safety-of-plerixafor-for-the-mobilization-collection-of-peripheral-hematopoietic-stem-cells-for-autologous-transplantation-in-japanese-patients-with-multiple-myeloma
#19
Masaki Ri, Kosei Matsue, Kazutaka Sunami, Chihiro Shimazaki, Akio Hayashi, Yoshinori Sunaga, Toru Sasaki, Kenshi Suzuki
To evaluate the efficacy and safety of plerixafor for the mobilization/collection of peripheral hematopoietic stem cells (HSCs) for autologous transplantation in Japanese patients with multiple myeloma (MM). In a randomized study, patients received G-CSF (filgrastim, 400 µg/m(2)/day) for 4 days prior to the first dose of plerixafor. Starting on Day 4 evening and for up to 4 days, patients received either plerixafor (240 µg/kg/day) + G-CSF group (PG group) or G-CSF alone (G group). Daily apheresis started on Day 5 for up to 4 days, or until ≥6 × 10(6) CD34+ cells/kg were collected...
May 19, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28496091/mobilization-of-hematopoietic-stem-cells-for-hematopoietic-cells-autologous-transplantation-with-use-of-plerixafor
#20
Krzysztof Gawroński, Piotr Rzepecki, Waldemar Sawicki, Jarosław Wajs
BACKGROUND To increase the number of circulating hematopoietic stem cells (HSC) in the blood, mobilization treatments are currently being used. G-CSF and G-CSF plus chemotherapy are the most common methods of hematopoietic stem cells separation used in Poland. MATERIAL AND METHODS We observed patients who failed an effective hematopoietic stem cell mobilization with G-CSF or with G-CSF plus chemotherapy. The separation was considered unsuccessful if within a period of 4 consecutive days of separation, the number of obtained CD 34+ cells was lower than 2...
May 12, 2017: Annals of Transplantation: Quarterly of the Polish Transplantation Society
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