Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Unregulated FGF signaling affects endochondral ossification and long bone growth, causing several genetic forms of human dwarfism. One major mechanism by which FGFs regulate endochondral bone growth is through their inhibitory effect on chondrocyte proliferation. Because mice with targeted mutations of the retinoblastoma (Rb)-related proteins p107 and p130 present severe endochondral bone defects with excessive chondrocyte proliferation, we have investigated the role of the Rb family of cell cycle regulators in the FGF response. Using a chondrocyte cell line, we found that FGF induced a rapid dephosphorylation of all three proteins of the Rb family (pRb, p107, and p130) and a blockade of the cells in the G1 phase of the cell cycle. This cell cycle block was reversed by inactivation of Rb proteins with viral oncoproteins such as polyoma large T (PyLT) antigen and Adenovirus E1A. Expression of a PyLT mutant that efficiently binds pRb, but not p107 and p130, allowed the cells to be growth inhibited by FGF, suggesting that pRb itself is not involved in the FGF response. To investigate more precisely the role of the individual Rb family proteins in FGF-mediated growth inhibition, we used chondrocyte micromass culture of limb bud cells isolated from mice lacking Rb proteins individually or in combination. Although wild-type as well as Rb-/- chondrocytes were similarly growth inhibited by FGF, chondrocytes null for p107 and p130 did not respond to FGF. Furthermore, FGF treatment of metatarsal bone rudiments obtained from p107-/-;p130-/- embryos failed to inhibit proliferation of growth plate chondrocytes, whereas rudiments from p107-null or p130-null embryos showed only a slight inhibition of growth. Our findings indicate that p107 and p130, but not pRb, are critical effectors of FGF-mediated growth inhibition in chondrocytes.
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PMID:FGF signaling targets the pRb-related p107 and p130 proteins to induce chondrocyte growth arrest. 1217 46

We compared native Adenoviral (Ad) vectors to a basic Fibroblast Growth Factor-retargeted Adenovirus (FGF2-Ad) for gene delivery into a diverse panel of lung cancer cells in vitro and xenografts in vivo. Cells were first evaluated for vector-specific receptor expression. Marked variations of surface coxsackie-adenovirus receptor (CAR), but relatively similar levels of alpha v integrin and FGF receptor expression were evident. Transduction efficiency by Ad directly correlated (R = 0.77, 95% CI 0.28-0.94, P = 0.0085) with CAR, but not with alpha v integrin expression. Transduction efficiency by FGF2-Ad did not correlate with the measured FGF receptor expression. Blocking studies indicated that gene transfer by FGF2-Ad occurred by a CAR-independent pathway, and could be inhibited by free FGF in a dose-dependent manner. Ad-antiserum inhibited FGF2-Ad gene transfer, suggesting that the Ad-component was needed for post-entry DNA-delivery. Soluble heparin sulfate proteoglycans (HSPG) or alpha v integrin blockers marginally decreased FGF2-Ad transduction. Both Ad and FGF2-Ad equally transduced CAR-positive non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells. By contrast, FGF2-Ad had a distinct transduction advantage in CAR-deficient NSCLC cells. This improvement in transduction of CAR-deficient cells by FGF2-Ad persisted in vivo. These data justify the need for an improved FGF2-Ad vector for clinical use in CAR-deficient lung cancer.
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PMID:Gene transfer mediated by native versus fibroblast growth factor-retargeted adenoviral vectors into lung cancer cells. 1562 75

The lipid-peroxidating enzyme, 15-lipoxygenase (LO)-1 and its metabolite, 13-S-hydroxyoctadecadienoic acid (13-S-HODE), likely contribute to prostate tumorigenesis. Thus, this study evaluated adenovirus-mediated overexpression of 15-LO-1 on normal mouse prostate. Adenovirus expressing either human 15-LO-1 tagged with green fluorescent protein (GFP) or GFP alone was orthotopically injected into the dorsolateral prostates of C57BL/6 mice, three times over the course of 60 days. On day 90, pathological changes in prostate tissue were assessed by hematoxylin and eosin (H&E) staining. Expression of the proliferation marker Ki-67 was evaluated by immunohistochemistry and expression of angiogenesis markers were analyzed by an antibody array. Based on the latter study, immunoprecipitation analysis was used to measure the effect of 13-S-HODE, with or without conditioned media, on fibroblast growth factor-a and b (FGF-a and FGF-b) expression in human PrEC (normal prostate epithelial), PrSMC (normal prostate smooth muscle) and PrSC (normal prostate stromal) lines. Expression of viral 15-LO-1-GFP, but not GFP alone, resulted in the development of a prostate intraepithelial neoplasia (PIN)-like phenotype with increased expression of Ki-67. Aberrant 15-LO-1 expression also induced the angiogenic markers FGF-a and FGF-b. Human PrEC, PrSMC and PrSC lines demonstrated an increase in FGF-b expression upon stimulation with 13-S-HODE, which was further increased by the addition of conditioned media from the epithelial or smooth muscle cells. Using adenoviral mediated 15-LO-1 gene delivery, this study suggests that aberrant 15-LO-1 overexpression in normal prostate can trigger events leading to prostate epithelial and stromal cell proliferation. Thus, our findings demonstrate the effectiveness of this viral system for 15-LO-1 expression studies in tissues.
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PMID:Orthotopic expression of human 15-lipoxygenase (LO)-1 in the dorsolateral prostate of normal wild-type C57BL/6 mouse causes PIN-like lesions. 1699 27