Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gamma-irradiation of plateau phase cultures of the clonal murine bone marrow stromal cell line D2XRII followed by cocultivation of a clonal interleukin 3 (IL-3) (granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent hematopoietic progenitor cell line FDC-P1JL26 results in a significant increase in "cobblestone islands" of attachment and emergence of subclonal factor-independent malignant sublines. Biochemical purification of conditioned medium from irradiated D2XRII cells yielded a 75,000-dalton glycoprotein termed leukemogenic stromal factor (LSF) that was neutralized by a polyclonal antiserum to murine macrophage colony-stimulating factor (M-CSF). A monoclonal antibody to the murine M-CSF receptor (c-fms) neutralized the biological activity of this molecule in a manner comparable to its effect on recombinant human or murine M-CSF. FDC-P1JL26 parent cells were positive for Ly5, MEL-14, mGR, VLA-4, PGP-1 (CD44), and Thy1.2. After culture in LSF, Thy1.2, MEL-14, and mGR became undetectable; however, significant cell surface MAC-1 antigen and c-fms (M-CSF receptor) were expressed. Neither line was positive for Ly6, Ly22, I-CAM-1, or B220 antigen. LSF-precultured FDC-P1JL26 cells transferred as single cells to microwell culture with 5000-cGy-irradiated D2XRII cells revealed a 60-fold increase in frequency of cobblestone island formation and evolution of factor-independent subclones compared to the parent line. Both parent and LSF-precultured cells became factor independent at a 100-fold lower frequency if kept in suspension in LSF in the absence of stromal cells. Antiserum to M-CSF or monoclonal antibody to the murine M-CSF receptor (c-fms) did not inhibit or displace cobblestone island formation by either clone of FDC-P1 on irradiated stromal cells indicating a mechanism of binding not involving the M-CSF receptor. However, anti-serum to the M-CSF receptor inhibited growth of one factor-independent subclone. In separate studies, a subclone of IL-3-dependent 32Dc13 cells, expressing the transfected murine c-fms protooncogene but not the parent 32Dc13 cell line or another subclone expressing the transfected gene for the human M-CSF receptor, showed adherence and became factor independent when cocultivated with irradiated D2XRII stromal cells. Thus, irradiated stromal cells bind M-CSF receptor-positive hematopoietic progenitor cells and induce c-fms-dependent factor-independent tumorigenic subclones. The cellular interactions in this model may be relevant to gamma-irradiation leukemogenesis in vivo.
 ...
PMID:Humoral and cell surface interactions during gamma-irradiation leukemogenesis in vitro. 153 94

We assessed the expression of the adhesion molecules leukocyte function antigen-1 (LFA-1, CD11a), intercellular adhesion molecule-1 (ICAM-1, CD54), homing-associated cell adhesion molecule (H-CAM, CD44), and c-kit (stem cell factor receptor) on the CD34+ progenitor population from the leukapheresis products of 23 patients (LP CD34+). For blood stem cell collection granulocyte colony-stimulating factor (G-CSF) or interleukin-3/granulocyte-macrophage colony-stimulating factor (IL-3/GM-CSF) was administered after cytotoxic chemotherapy. Furthermore, bone marrow- and blood-derived CD34+ progenitor cells from 6 normal volunteers (BM and PB CD34+) were analyzed. LFA-1 expression was higher on PB CD34+ (88.2 +/- 2.5%, mean +/- SEM) than on BM CD34+ (75.3 +/- 4.3%). Following cytokine administration, LFA-1 was expressed on only 59.7 +/- 3.7% of LP CD34+ at a low fluorescence intensity, suggesting that down-regulation of LFA-1 may facilitate the egress of cells from the bone marrow and prolong their circulation. In contrast, ICAM-1 was weakly positive on CD34+ cells from all sources. CD44 was expressed on the vast majority of CD34+ cells (> 95%) in all samples studied. The highest proportion of CD34+ cells costaining for c-kit was found in normal bone marrow (32.2 +/- 3.3%). In normal peripheral blood and after cytokine mobilization, fewer of the CD34+ cells weakly expressed c-kit (< 15%). The low percentage and level of c-kit expression may indicate that the majority of cytokine-mobilized CD34+ cells are lineage-committed progenitor cells, as reflected by the coexpression pattern for CD38, HLA-DR, and CD33.
 ...
PMID:Expression of adhesion molecules and c-kit on CD34+ hematopoietic progenitor cells: comparison of cytokine-mobilized blood stem cells with normal bone marrow and peripheral blood. 752 8

In this retrospective study, we assessed the impact of each of three consecutive cycles of conventional-dose chemotherapy on CD34+ cells, colony-forming units granulocyte-macrophage (CFU-GM), and contaminating breast cancer cells collected in the leukapheresis products of patients with metastatic breast cancer. The patients subsequently underwent high-dose chemotherapy followed by autologous blood progenitor cell transplantation. We analyzed 172 leukapheresis products from 17 patients and have correlated the long-term clinical outcome with tumor cell contamination. The induction chemotherapy regimen consisted of three cycles of cyclophosphamide 750 mg/m2 i.v., epirubicin 100 mg/m2, and 5-fluorouracil (5-FU) 750 mg/m2 i.v., followed by 5 microg/kg body weight of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) daily until leukapheresis was completed. An average of 10 leukapheresis products (three to four collections after each cycle of chemotherapy) were obtained from each patient. Numbers of CD34+ cells, CFU-GM, and mononuclear cells (MNCs) in the leukapheresis products were determined at the time of collection. Aliquots from the same products were frozen and breast cancer cells were detected by immunocytochemistry with a cocktail of anti-cytokeratin antibodies (AE-1, AE-3, CAM 5.2, Keratin 8+18+19) using a standardized immunoalkaline phosphatase method. A minimum of 10(6) cells were examined by light microscopy and by at least two blinded observers. Cells were considered positive when immunostaining was detected in the cytoplasm and on the cell membrane, and cellular morphology was consistent with a malignant phenotype. Of the 172 samples analyzed, 13 of 57 (23%) leukapheresis products collected after cycle I were positive for tumor cells; 3 of 60 (5%) after cycle II; and 4 of 55 (7%) after cycle III. The likelihood of contamination by breast cancer cells after cycle I was significantly higher than after subsequent cycles of chemotherapy (p = 0.0052). Simultaneously, there was a significant decrease in quantity of CD34+ cells and CFU-GM (p < 0.0001 for both comparisons). Our study indicated that leukapheresis products collected after the second or third cycles of induction chemotherapy carry a significantly lower likelihood of tumor cell contamination, albeit the quantity of CD34+ cells or CFU-GM collected was also significantly reduced.
 ...
PMID:Decrease in tumor cell contamination and progenitor cell yield in leukapheresis products after consecutive cycles of chemotherapy for breast cancer treatment. 950 99