Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that the myeloid progenitor cell line 32Dc13 transduced with mIL-12 cDNAs (32DIL-12 cells) induces IFN-gamma and NK-cell-mediated cytotoxicity in vivo. Since systemic therapy with recombinant IL-12 protein has been shown to produce moderate to severe toxic side effects we examined whether IL-12 gene therapy with hematopoietic progenitor cells also induces systemic toxicities that are commonly associated with the administration of rIL-12 protein. Injection of large doses of IL-12 secreting 32DIL-12 cells (5 to 6 x 10(7) cells) significantly reduced mortality in mice injected with a lethal dose of 32Dp210 myeloid leukemia cells. More importantly, injection of similar doses of transduced cells failed to reduce body weight significantly or produce other visible signs of toxicity, i.e., fur ruffling or lethargy. There was no evidence of hematologic or hematopoietic toxicity resulting from the injection of transduced cells. In addition, microscopic examination of liver, kidney, lung, and intestine of mice injected with transduced cells revealed the absence of tissue necrosis or inflammatory response in any of these organs. Finally, 32DIL-12 cells were not found to interfere with the engraftment of syngeneic bone marrow transplant or the hematopoietic reconstitution of irradiated mice. These results demonstrate that IL-12 gene therapy with hematopoietic progenitor cells is nontoxic and provide a rationale for exploring the feasibility of treating minimal residual leukemia with IL-12 gene therapy.
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PMID:IL-12 gene therapy of leukemia with hematopoietic progenitor cells without the toxicity of systemic IL-12 treatment. 1116 74

This manuscript reports on five cases of spontaneous myelogenous leukemia, similar to human disease, occurring within highly inbred, histocompatible sublines of Massachusetts General Hospital (MGH) MHC-defined miniature swine. In cases where a neoplasm was suspected based on clinical observations, samples were obtained for complete blood count, peripheral blood smear, and flow cytometric analysis. Animals confirmed to have neoplasms were euthanized and underwent necropsy. Histological samples were obtained from abnormal tissues and suspect lesions. The phenotype of the malignancies was assessed by flow cytometric analysis of processed peripheral blood mononuclear cells and affected tissues. Five cases of spontaneous myeloid leukemia were identified in adult animals older than 30 months of age. All animals presented with symptoms of weight loss, lethargy, and marked leukocytosis. At autopsy, all animals had systemic disease involvement and presented with severe hepatosplenomegaly. Three of the five myelogenous leukemias have successfully been expanded in vitro. The clustered incidence of disease in this closed herd suggests that genetic factors may be contributing to disease development. Myelogenous leukemia cell lines established from inbred sublines of MGH MHC-defined miniature swine have the potential to be utilized as a model to evaluate therapies of human leukemia.
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PMID:Myelogenous leukemia in adult inbred MHC-defined miniature swine: a model for human myeloid leukemias. 2007 39