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)

Currently, no effective therapy exists for patients suffering from progressive medullary thyroid carcinoma (MTC), a calcitonin (CT)-secreting C cell tumor. As CT, which arises from the precursor protein preprocalcitonin (PPCT), is expressed by almost all MTC cases, these molecules may represent target antigens for immunotherapy against MTC. In our study we investigated whether DNA immunization is able to induce cellular and humoral immune responses against human PPCT (hPPCT) in mice. Antigen-encoding expression plasmids were delivered intradermally by gene gun. One group of mice received DNA encoding hPPCT only. Two groups were coinjected with mouse cytokine genes. We observed in lymphocyte proliferative assays substantial proliferation against hPPCT in mice coinjected with the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene, in contrast to mice vaccinated with hPPCT expression plasmid only. In addition, codelivery of the GM-CSF gene augmented the frequency of anti-hPPCT antibody seroconversions in sera of immunized animals, as shown by enzyme-linked immunosorbent assay. These results illustrate that cellular and humoral immune responses against hPPCT can be generated by DNA immunization and increased by coinjection of the GM-CSF gene. Our findings may have implications for the use of DNA immunization as a potential novel immunotherapeutic treatment for patients suffering from progressive MTC.
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PMID:Induction of a cellular and humoral immune response against preprocalcitonin by genetic i: a potential new treatment for medullary thyroid carcinoma. 1118 14

Thyroid tumors producing colony-stimulating factors associated with neutrophilia and/or eosinophilia are very rare and almost all of them concern anaplastic thyroid cancer. Only one case of papillary thyroid carcinoma associated with neutrophilia and one case of medullary thyroid carcinoma associated with eosinophilia have been reported. In this report a 72-year old male patient with metastatic papillary thyroid carcinoma associated with neutrophilia and eosinophilia is described. While investigating the cause of neutrophilia and eosinophilia, a blind bone marrow biopsy of the posterior iliac crest was performed, which showed infiltration by papillary thyroid carcinoma. High blood levels of granulocyte-macrophage colony-stimulating factor (GM-csF) were found using an enzyme-linked immunosorbent assay. As other causes of neutrophilia and eosinophilia were excluded, we assumed that these were paraneoplastic manifestations induced by GM-csF produced by the thyroid tumor. the disease progressed rapidly, despite appropriate treatment which included thyroidectomy and postoperative radioactive (131)I administration. the patient died 11 months after diagnosis because of extensive lung metastasis. Neutrophilia and eosinophilia were stable findings, while serum thyroglobulin levels remained elevated throughout the follow-up period. to our knowledge, this is the first report of a patient with metastatic papillary thyroid carcinoma in whom neutrophilia and eosinophilia associated with high circulating levels of GM-csF were detected.
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PMID:Papillary thyroid carcinoma producing granulocyte-macrophage colony-stimulating factor is associated with neutrophilia and eosinophilia. 1717 6

The existence of inherited aggressive forms of medullary thyroid carcinoma (MTC) and their resistance to classical therapies make it a prime candidate for adoptive immunotherapy. Highly potent antigen-presenting cells, namely dendritic cells (DCs), may serve as an interesting tool for anticancer vaccination. Here we report on the IN VITRO findings of a vaccination trial in five MTC patients, who were treated with a new DC generation protocol consisting of granulocyte-macrophage colony-stimulating factor and interferon-alpha (IFN-DCs). These cells were pulsed with tumor-specific calcitonin and administered twice. In two patients who responded to therapy we found a large increase (in mean 2.9+/-1.9%) of antigen-specific IFN-gamma-secreting CD4+ cells as well as an increase of granzyme B positive CD8+ cells (mean 2.2+/-0.2%) in the peripheral blood. In parallel, a decrease of CD4+/CD25+/FoxP3+ regulatory T cells was seen. Importantly, IN VITRO stimulation of PBMC with 10 different 15mer calcitonin peptides resulted in the identification of two HLA class II epitope regions within the central part of full-length calcitonin. These data were in accordance with the results drawn from the computer-based algorithm epitope prediction software SYFPEITHI. Measurement of different pro- and anti-angiogenic factors did not allow for a distinct outcome of prediction of the treated patients. In summary, we have demonstrated that immunization with IFN-DCs leads to a tumor epitope-specific immune response in MTC patients and may, therefore, represent a promising tool for future vaccination trials.
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PMID:Dendritic cell vaccination induces tumor epitope-specific Th1 immune response in medullary thyroid carcinoma. 1828 28