scholarly journals 814-4 Mobilization of bone marrow cells (stem cells) by granulocyte-colony stimulating factor associated or not with intracoronary stem infusion improves exercise capacity and quality of life in severe heart failure

2004 ◽  
Vol 43 (5) ◽  
pp. A187
Author(s):  
Edimar A Bocchi ◽  
Fernando Bacal
2006 ◽  
Vol 24 (33) ◽  
pp. 5271-5276 ◽  
Author(s):  
Brian H. Kushner ◽  
Kim Kramer ◽  
Shakeel Modak ◽  
Nai-Kong V. Cheung

Purpose To report on an irinotecan and temozolomide regimen for neuroblastoma (NB). Quality of life and minimizing toxicity were major considerations. Patients and Methods The plan stipulated 5-day courses of irinotecan 50 mg/m2 (1-hour infusion) and temozolomide 150 mg/m2 (oral) every 3 to 4 weeks, with a pretreatment platelet count more than 30,000/μL. Granulocyte colony-stimulating factor was used when the absolute neutrophil count was less than 1,000/μL. Results Forty-nine NB patients received 1 to 15 courses (median, 5). Gastrointestinal and myelosuppressive toxicities were readily managed. Lymphocyte responses to phytohemagglutinin after 2 to 10 courses (median, 3.5) were normal in 10 of 10 patients treated after nonimmunosuppressive therapy, and normalized in five of seven patients first treated less than 2 months after high-dose alkylators. Of 19 patients treated for refractory NB and assessable for response, nine showed evidence of disease regression, including two complete responses and seven objective responses. Of 17 patients treated for progressive disease, three showed evidence of disease regression, including one partial response and two objective responses. Multiple courses entailed no cumulative toxicity and controlled disease for prolonged periods in many patients, including some who were unable to complete prior treatments because of hematologic, infectious, cardiac, or renal problems. Conclusion This regimen has anti-NB activity, spares vital organs, is feasible with poor bone marrow reserve, causes limited immunosuppression, and allows good quality of life.


2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Wen-Ching Tzaan ◽  
Hsien-Chih Chen

Intervertebral disc (IVD) degeneration is a multifactorial process that is influenced by contributions from genetic predisposition, the aging phenomenon, lifestyle conditions, biomechanical loading and activities, and other health factors (such as diabetes). Attempts to decelerate disc degeneration using various techniques have been reported. However, to date, there has been no proven technique effective for broad clinical application. Granulocyte colony-stimulating factor (GCSF) is a growth factor cytokine that has been shown to enhance the availability of circulating hematopoietic stem cells to the brain and heart as well as their capacity for mobilization of mesenchymal bone marrow stem cells. GCSF also exerts significant increases in circulating neutrophils as well as potent anti-inflammatory effects. In our study, we hypothesize that GCSF can induce bone marrow stem cells differentiation and mobilization to regenerate the degenerated IVD. We found that GCSF had no contribution in disc regeneration or maintenance; however, there were cell proliferation within end plates. The effects of GCSF treatment on end plates might deserve further investigation.


Blood ◽  
1990 ◽  
Vol 75 (3) ◽  
pp. 563-569 ◽  
Author(s):  
G Molineux ◽  
Z Pojda ◽  
TM Dexter

Abstract Recombinant human granulocyte colony-stimulating factor (rhG-CSF) induces leukocytosis in vivo in both intact and splenectomized mice. Full dose response data showed a plateau in this effect at doses over 500 micrograms rhG-CSF/kg body weight/d in intact mice. The effect is magnified in splenectomized mice, where leukocyte numbers reach 100 x 10(6) mL after 4 days' treatment at 250 micrograms/kg/d. Further hematopoietic precursor populations are also affected in both marrow and the spleen; in general, marrow parameters were depressed, while splenic populations were enlarged. In splenectomized mice, both blood- borne stem cells were enhanced, and foci of extramedullary hematopoiesis were enlarged in addition to the effects seen in intact mice. In the marrow of splenectomized and intact mice treated with a high dose of G-CSF, erythroid suppression in the marrow was confirmed with radioactive iron. Our studies confirm and extend previous work on the mode of action of G-CSF, and indicate that side effects of high dose G-CSF therapy might include erythroid suppression in the bone marrow.


2006 ◽  
Vol 26 (21) ◽  
pp. 8052-8060 ◽  
Author(s):  
Ewa Sicinska ◽  
Young-Mi Lee ◽  
Judith Gits ◽  
Hirokazu Shigematsu ◽  
Qunyan Yu ◽  
...  

ABSTRACT The proliferation of neutrophil granulocyte lineage is driven largely by granulocyte colony-stimulating factor (G-CSF) acting via the G-CSF receptors. In this study, we show that mice lacking cyclin D3, a component of the core cell cycle machinery, are refractory to stimulation by the G-CSF. Consequently, cyclin D3-null mice display deficient maturation of granulocytes in the bone marrow and have reduced levels of neutrophil granulocytes in their peripheral blood. The mutant mice are unable to mount a normal response to bacterial challenge and succumb to microbial infections. In contrast, the expansion of hematopoietic stem cells and lineage-committed myeloid progenitors proceeds relatively normally in mice lacking cyclin D3, revealing that the requirement for cyclin D3 function operates at later stages of neutrophil development. Importantly, we verified that this requirement is specific to cyclin D3, as mice lacking other G1 cyclins (D1, D2, E1, or E2) display normal granulocyte counts. Our analyses revealed that in the bone marrow cells of wild-type mice, activation of the G-CSF receptor leads to upregulation of cyclin D3. Collectively, these results demonstrate that cyclin D3 is an essential cell cycle recipient of G-CSF signaling, and they provide a molecular link of how G-CSF-dependent signaling triggers cell proliferation.


Blood ◽  
1996 ◽  
Vol 88 (11) ◽  
pp. 4139-4148 ◽  
Author(s):  
KJ Grzegorzewski ◽  
KL Komschlies ◽  
JL Franco ◽  
FW Ruscetti ◽  
JR Keller ◽  
...  

Abstract Administration of recombinant human interleukin-7 (rhIL-7) to mice increases the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakaryocyte macrophage [CFU-GEMM]) from the bone marrow (BM) to peripheral organs, including blood, and also increases the number of primitive progenitor and stem cells in the peripheral blood (PB). We now report that combined treatment of mice with rhIL-7 and recombinant human granulocyte-colony stimulating factor (rhG-CSF) stimulates a twofold to 10-fold increase in the total number of PB CFU-c, and a twofold to fivefold increase in the total number of PB CFU-spleen at day 8 (CFU-S8) over the increase stimulated by rhIL-7 or rhG-CSF alone. In addition, the quality of mobilized cells with trilineage, long-term marrow-repopulating activity is maintained or increased in mice treated with rhIL-7 and rhG-CSF compared with rhIL-7 or rhG-CSF alone. These differences in mobilizing efficiency suggest qualitative differences in the mechanisms by which rhIL-7 and rhG-CSF mobilize progenitor cells, in fact, the functional status of progenitor cells mobilized by rhIL-7 differs from that of cells mobilized by rhG-CSF in that the incidence of actively cycling (S-phase) progenitors obtained from the PB is about 20-fold higher for rhIL-7-treated mice than for mice treated with rhG-CSF. These results suggest the use of rhIL-7-mobilized progenitor/stem cells for gene-modification and tracking studies, and highlight different functions and rates of repopulation after reconstitution with PB leukocytes obtained from mice treated with rhIL-7 versus rhG-CSF.


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