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Gretchen M Unger

Publications and source records attributed to Gretchen M Unger.

2 recordsLinked to original sources
PubMed2005

Improving surgical wound healing with basic fibroblast growth factor after radiation.

OBJECTIVES/HYPOTHESIS: Delayed wound healing in surgical patients who have received previous irradiation continues to be a significant problem. We investigated whether radiation decreases basic fibroblast growth factor (bFGF) production in skin and whether supplemental bFGF can improve irradiated postsurgical soft tissue healing. STUDY DESIGN: Experimental study in the porcine skin flap model. METHODS: Pigs were subjected to orthovoltage radiation (1,300 cGy). To test whether radiation alters bFGF production in skin, semiquantitation of bFGF message was compared in irradiated and nonirradiated skin by reverse transcription-polymerase chain reaction (RT-PCR). To determine whether supplemental bFGF can improve postsurgical soft tissue healing after radiation, bFGF was given intravenously or intracuticularly preoperatively. To investigate whether additional oxygen tissue levels would modify the effects of supplemental bFGF, one test group received hyperbaric oxygen. Six weeks later, 108 skin flaps (random and arterial) were created in 27 pigs and monitored over 2 weeks. Tissues were analyzed for flap viability, vascularity, endothelial cell apoptosis by caspase-3 activation, and histologic analysis. RESULTS: Radiation statistically increased endothelial cell apoptosis in porcine skin by 650%. Radiation also significantly reduced bFGF message by 75% in porcine skin by RT-PCR analysis. Supplemental intravenous bFGF in irradiated tissue significantly increased skin flap viability by 25% compared with controls (P < .001). Intravenous bFGF also significantly reduced gastrointestinal side effects from irradiation by 50% compared with controls. BFGF treatment induced a trend to decrease endothelial cell apoptosis in irradiated skin, but this was not statistically significant. Histologically, the intravenous bFGF-treated flaps had similar cellularity, fibroblasts, and extracellular acid mucopolysaccharides as controls. When bFGF was administered by intracuticular injection with and without hyperbaric oxygen, skin flap survival and flap vascularity were similar to controls. CONCLUSIONS: Decreased local levels of bFGF in skin may play an important role in the delayed healing of irradiated wounds. Radiation appears to decrease bFGF production by significantly reducing bFGF message in irradiated tissue. Supplemental intravenous bFGF reduced irradiated soft tissue injury and improved random skin flap viability in this porcine model. More studies are needed to investigate the effects of bFGF in the surgical healing of irradiated wounds.

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PubMed2004

Induction of apoptosis by antisense CK2 in human prostate cancer xenograft model.

Protein serine/threonine kinase CK2 (formerly casein kinase 2) is a ubiquitous protein kinase that plays key roles in cell growth, proliferation, and survival. We have shown previously that its molecular down-regulation induces apoptosis in cancer cells in culture. Here, we have employed a xenograft model of prostate cancer to extend these studies to determine whether antisense CK2alpha evokes a similar response in vivo. A single dose of antisense CK2alpha oligodeoxynucleotide given directly into the PC3-LN4 xenograft tumor in nude mouse induced a dose- and time-dependent tumor cell death in vivo. The tumor was completely resolved at the higher tested dose of the antisense. Cell death was due to apoptosis and correlated with a potent down-regulation of the CK2alpha message and loss of CK2 from the nuclear matrix in the xenograft tissue as well as in cancer cells in culture. These observations accorded with several of the earlier studies indicating that loss of CK2 from the nuclear matrix is associated with induction of apoptosis. Comparison of the effects of antisense CK2alpha oligodeoxynucleotide on cancer versus normal or noncancer cells showed that the concentration of antisense CK2alpha that elicited extensive apoptosis in tumor cells in culture or xenograft tumors in vivo had a relatively small or minimal effect on noncancer cells in culture or on normal prostate gland subjected to orthotopic injection of antisense oligodeoxynucleotide in vivo. The basis for the difference in sensitivity of cancer versus noncancer cells to antisense CK2alpha is unknown at this time; however, this differential response under similar conditions of treatment may be significant in considering the potential feasibility of targeting the CK2 signal for induction of apoptosis in cancer cells in vivo. Although much further work will be needed to establish the feasibility of targeting CK2 for cancer therapy, to our knowledge, this is the first report to provide important new evidence as an initial "proof of principle" for the potential application of antisense CK2alpha in cancer therapy, paving the way for future detailed studies of approaches to targeting CK2 in vivo to induce cancer cell death.

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