Authors: | Lin, H.; de Stanchina, E.; Zhou, X. K.; Hong, F.; Seidman, A.; Fornier, M.; Xiao, W. L.; Kennelly, E. J.; Wesa, K.; Cassileth, B. R.; Cunningham Rundles, S. |
Article Title: | Maitake beta-glucan promotes recovery of leukocytes and myeloid cell function in peripheral blood from paclitaxel hematotoxicity |
Abstract: | Bone marrow myelotoxicity is a major limitation of chemotherapy. While granulocyte colony stimulating factor (G-CSF) treatment is effective, alternative approaches to support hematopoietic recovery are sought. We previously found that a beta-glucan extract from maitake mushroom Grifola frondosa (MBG) enhanced colony forming unit-granulocyte monocyte (CFU-GM) activity of mouse bone marrow and human hematopoietic progenitor cells (HPC), stimulated G-CSF production and spared HPC from doxorubicin toxicity in vitro. This investigation assessed the effects of MBG on leukocyte recovery and granulocyte/monocyte function in vivo after dose intensive paclitaxel (Ptx) in a normal mouse. After a cumulative dose of Ptx (90-120 mg/kg) given to B6D2F1mice, daily oral MBG (4 or 6 mg/kg), intravenous G-CSF (80 μg/kg) or Ptx alone were compared for effects on the dynamics of leukocyte recovery in blood, CFU-GM activity in bone marrow and spleen, and granulocyte/monocyte production of reactive oxygen species (ROS). Leukocyte counts declined less in Ptx + MBG mice compared to Ptx-alone (p = 0.024) or Ptx + G-CSF treatment (p = 0.031). Lymphocyte levels were higher after Ptx + MBG but not Ptx + G-CSF treatment compared to Ptx alone (p < 0.01). MBG increased CFU-GM activity in bone marrow and spleen (p < 0.001, p = 0.002) 2 days after Ptx. After two additional days (Ptx post-day 4), MBG restored granulocyte/monocyte ROS response to normal levels compared to Ptx-alone and increased ROS response compared to Ptx-alone or Ptx + G-CSF (p < 0.01, both). The studies indicate that oral MBG promoted maturation of HPC to become functionally active myeloid cells and enhanced peripheral blood leukocyte recovery after chemotoxic bone marrow injury. © 2010 Springer-Verlag. |
Keywords: | cancer chemotherapy; controlled study; unclassified drug; human cell; dose response; nonhuman; paclitaxel; chemotherapy; animal cell; mouse; animal; metabolism; animals; mice; cell function; bone marrow; bone marrow suppression; cell maturation; spleen; blood toxicity; granulocyte macrophage colony stimulating factor; animal experiment; animal model; in vivo study; drug effect; pathology; cell line, tumor; immunology; drug antagonism; drug mechanism; drug combination; drug therapy, combination; tumor cell line; reactive oxygen species; reactive oxygen metabolite; mushroom; bone marrow cell; leukocyte count; mouse strain; monocyte; beta glucan; recombinant granulocyte colony stimulating factor; grifola frondosa extract; maitake extract; grifola frondosa; grifola; cell strain mcf 7; leukocyte; oxidation reduction reaction; oxidation-reduction; granulocyte; beta-glucan; colony forming unit gm; beta-glucans; colony forming unit; carbohydrate diet; granulocyte-macrophage colony-stimulating factor; bone marrow and leukocyte recovery; hematopoietic progenitor cells; hematotoxicity; fungal extract; leukopoiesis; dietary carbohydrates; granulocyte-macrophage progenitor cells; leukocytes |
Journal Title: | Cancer Immunology, Immunotherapy |
Volume: | 59 |
Issue: | 6 |
ISSN: | 0340-7004 |
Publisher: | Springer |
Date Published: | 2010-06-01 |
Start Page: | 885 |
End Page: | 897 |
Language: | English |
DOI: | 10.1007/s00262-009-0815-3 |
PUBMED: | 20140432 |
PROVIDER: | scopus |
PMCID: | PMC3268513 |
DOI/URL: | |
Notes: | --- - "Export Date: 20 April 2011" - "CODEN: CIIMD" - "Source: Scopus" |