Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have created a novel cellular vehicle for gene therapy of malignant gliomas by transfection of murine bone marrow stroma cells (MSCs) with a cDNA encoding epidermal growth factor receptor (EGFR). These cells (EGFR-MSCs) demonstrate enhanced migratory responses toward glioma-conditioned media in comparison to primary MSCs in vitro. Enhanced migration of EGFR-MSC was at least partially dependent on EGF-EGFR, PI3-, MAP kinase kinase, and MAP kinases, protein kinase C, and actin polymerization. Unlike primary MSCs, EGFR-MSCs were resistant to FasL-mediated cytotoxicity and were capable of stimulating allogeneic mixed lymphocyte reaction, suggesting EGFR-MSCs possess suitable characteristics as vehicles for brain tumor immuno-gene therapy. Following injection at various sites, including the contralateral hemisphere in the brain of syngeneic mice, EGFR-MSCs were able to migrate toward GL261 gliomas or B16 melanoma in vivo. Finally, intratumoral injection with EGFR-MSC adenovirally engineered to secrete interferon-alpha to intracranial GL261 resulted in significantly prolonged survival in comparison to controls. These data indicate that EGFR-MSCs may serve as attractive vehicles for infiltrating brain malignancies such as malignant gliomas.
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PMID:Epidermal growth factor receptor-transfected bone marrow stromal cells exhibit enhanced migratory response and therapeutic potential against murine brain tumors. 1583 73

Purified B-cells from normal tonsils and from the peripheral blood of eight patients with B-chronic lymphocytic leukemia (B-CLL) were treated in vitro with the protein kinase C (PKC) activators TPA, Bryostatin 1 (Bryo), mezerein, with the calcium ionophore A23187, and with the cytokines interleukin-1/2, interferon-alpha/gamma, tumor necrosis factor. The induction of the lysosomal enzyme tartrate-resistant acid phosphatase (TRAP) was examined at the RNA (by Northern blotting analysis) and the protein level (by isoelectric focusing). TRAP mRNA and protein were induced by treatment with PKC activators while the combination of PKC stimulator and calcium ionophore was not effective, TRAP mRNA was detected as early as 2 hours after initiation of the culture. This induction of positivity for TRAP which is the enzymatic hallmark of hairy cell leukemia (HCL) by TPA or Bryo is consistent with the previously reported acquisition of HCL-type cellular features in TPA-driven CLL cells; CLL cells exposed to the double stimulus of TPA or Bryo + A23187 have previously been described to differentiate to plasmacytoid cells which is in accord with their remaining TRAP negative. The present data provide evidence that 1) B-CLL cells can be induced by direct stimulation of PKC to convert to HCL-type cells; 2) TPA/Bryo-exposed B-CLL cells display phenotypes different from those of cells treated with combinations containing calcium ionophore; 3) the phosphoinositol signal transduction pathway distal to PKC can be activated effectively in B-CLL cells; 4) Bryo, a new natural PKC activator, induces responses in CLL similar to those caused by TPA; 5) TRAP is an inducible indicator of cellular activation. These observations provide support for the idea that HCL and HCL-like cells might differentiate along a separate branch of B-cell lineage and might represent mature "activation end stage" cells.
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PMID:Differential expression of TRAP Isoenzyme in B-CLL Cells Treated with Different Inducers. 2745 94


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