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

Colony-stimulating factor-1 (CSF-1) is a member of the immediate early gene family, which is expressed in mitogen-stimulated quiescent fibroblasts. The biological effects of CSF-1 are multifaceted and include stimulation of the proliferation and differentiation of myeloid progenitors and activity of circulating monocytes and tissue-specific macrophages. Ablation of circulating levels of biologically active CSF-1 in mice leads to osteopetrosis and sterility, thus implicating a role for CSF-1 in bone remodeling and implantation. Identification of regulatory elements and cognate transcription factors that bind the csf-1 promoter and mediate such diverse expression patterns is of great interest. We identified a sequence element at -273 to -265 (relative to the transcription initiation site) in the murine csf-1 promoter, which contains overlapping consensus sequences for the Wilms' tumor protein (WT1), EGR-1, SP1, and SP3 proteins. WT1 and EGR-1 proteins produced in vitro bound to this sequence, and co-transfection of wt1 with a csf-1-cat reporter plasmid resulted in repression of promoter activity. Interestingly, nuclear extracts prepared from serum-stimulated C3H10T1/2 cells contained predominantly SP1 and SP3 binding activities, which recognized the -273 to -265 site. Thus repression of the csf-1 promoter by WT1 at this site may involve competition between SP1 family transcriptional activators and the WT1 repressor. Colony-stimulating factor-1 may be a physiologically relevant target gene for regulation by the WT1 transcription factor.
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PMID:Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus. 840 65

We describe the safety and immunogenicity of a combined vaccine of 2 leukemia-associated antigenic peptides, PR1 and WT1. Eight patients with myeloid malignancies received one subcutaneous dose each of PR1 and WT1 vaccines in Montanide adjuvant, with granulocyte-macrophage colony-stimulating factor. Patients were reviewed weekly for 4 weeks to monitor toxicity and immunologic responses. Toxicity was limited to grades 1 to 2. Using peptide/HLA-A 0201 tetramers and intracellular interferon-gamma staining, CD8(+) T cells against PR1 or WT1 were detected in 8 of 8 patients after a single vaccination. To monitor the kinetics of vaccine-induced CD8(+) T-cell responses and disease regression after vaccination, absolute PR1 and WT1(+)CD8(+) T-cell numbers and WT1 expression were studied weekly after vaccination. Responses occurred as early as 1 week after vaccination. After vaccination, the emergence of PR1 or WT1(+)CD8(+) T cells was associated with a decrease in WT1 mRNA expression as a marker of minimal residual disease, suggesting a vaccine-driven antileukemia effect. Conversely, loss of response was associated with reappearance of WT1 transcripts (P < .01). This is the first demonstration that a combined PR1 and WT1 vaccine is immunogenic. These results support further studies of combination immunization strategies in leukemia patients.
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PMID:Leukemia-associated antigen-specific T-cell responses following combined PR1 and WT1 peptide vaccination in patients with myeloid malignancies. 1787 4

A dendritic cell (DC)-based vaccine was combined with intensity-modulated radiotherapy (IMRT) or other conformal radiotherapy (RT), assuming minimal immunosuppression by such RT modalities. In this study, the outcomes in the first 40 patients are presented. The patients had recurrent, metastatic or locally advanced tumors. Nine had previously undergone full-course RT. Peripheral blood mononuclear cells obtained by leukapheresis were cultured with granulocyte-macrophage colony-stimulating factor, interleukin-4, OK-432 and prostaglandin E2 to generate DCs, which were pulsed with autologous tumor lysates or tumor-specific peptides, such as WT1. IMRT using tomotherapy, stereotactic irradiation or 3-dimensional conformal RT (3DCRT) was initially administered. The standard dose was 30 and 60 Gy in patients with and without previous RT, respectively. Every other week thereafter, up to a total of 7 times, DC vaccines were injected directly into the tumor (n=15) or administered intradermally when DCs were pulsed with tumor lysates or peptides. The tumor response was evaluated according to the response evaluation criteria in solid tumors (RECIST). RT and DC vaccines were well tolerated and there were no major complications. Three patients were not able to complete the planned DC therapy due to disease progression. For the 31 patients receiving full-dose RT, the response rate was 61% and for the 9 patients who had previously received RT, the response rate was 55%. In 9 patients, the tumor response outside the RT target volume was evaluable: 22% had a partial response (PR), 33% had stable disease (SD) and 44% had progressive disease (PD). In conclusion, a combination of IMRT (or 3DCRT) and DC vaccine is feasible and requires further investigation.
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PMID:Immune-maximizing (IMAX) therapy for cancer: Combination of dendritic cell vaccine and intensity-modulated radiation. 2464 23