[Show abstract][Hide abstract] ABSTRACT: Increasing incidence of carcinomas in the upper aero-digestive tract, both in Germany and in other European countries requires development of new preventive strategies. The cure rate at advanced tumor stages remains poor in spite of a variety of available therapeutic methods. In the present study the quantitative assessment of a pre-malignant mucosa lesion within a field cancerization was performed by means of immunocytochemical methods. This may allow individuals with an increased risk of developing malignant disease to be identified. Cytosmears taken from healthy buccal mucosa of tumor patients (n=50) and from healthy probands (n=100) with different tobacco and alcohol consumption levels were examined with regard to identifying increased expression of the proliferation markers (PCNA, MIB1), of the tumor suppressor gene product p53 as well as the oncogene product cyclin D1. There was a significant difference in expression of investigated proliferation markers between tumor patients and healthy probands (p<0.0001). When comparing the rate of positively marked cell nuclei to cigarette pack years the marker cyclin D1 and MIB1 show an increased rate in the groups with high tobacco consumption as compared to the group with a low exposure (p>0.05). It could be possible to use the marker MIB1 and cyclin D1 to screen risk groups, since the relative morbidity risk (odds ratio) increases (by 45-62 times) if the threshold value of 4 positively marked cell nuclei is exceeded.
[Show abstract][Hide abstract] ABSTRACT: Abnormal wound healing processes can result in hypertrophic scars and keloids. Transforming growth factor-beta1 (TGF-beta1) and hepatocyte growth factor/scatter factor (HGF/SF) are biphasic growth factor cytokines in physiologic and pathophysiologic conditions. Findings have shown TGF-beta1 to be pivotal in the formation of keloid tissue. Therefore, neutralizing antibodies may allow wound healing without keloid formation. As reported, TGF-beta1 is antagonized by HGF/SF. Some authors have reported that exogenous administration of HGF/SF prevented scar formation. Hence, this study targeted TGF-beta1 and determined the levels of HGF/SF in fibroblast cell culture. Keloid tissue was taken from seven patients. Another seven patients with mature nonhypertrophic scar served as controls. All tissues were cultured, and fibroblast cultures were used for further experiments. The TGF-beta1 antisense was administered at 3 and 6 micromol/ml, and HGF/SF levels were determined after 16, 24, and 48 h of incubation. The levels of HGF/SF showed significant differences after incubation with antisense oligonucleotides. The increasing antisense levels resulted in increased HGF/SF levels (up to 87.66 pg/ml after 48 h of incubation). In conclusion, targeting TGF-beta1 resulted in significantly increased levels of HGF/SF. The clinical relevance could include the use of locally administered HGF/SF in protein or gene form to minimize formation of keloids. Nevertheless, wound healing is the result of many interacting cytokines, so neutralizing or targeting one protein could result in no significant effect.
No preview · Article · Apr 2008 · Aesthetic Plastic Surgery
[Show abstract][Hide abstract] ABSTRACT: Eosinophilic chronic rhinosinusitis (ECRS) is one of the most common diseases worldwide. To date the underlying cause remains unclear and no drug has been accredited for first-line therapy. VCAM-1 has been reported to play a pivotal role in establishing ECRS. Other authors have reported that inflammatory cytokines may mediate changes in the underlying epithelium in the sinuses through hepatocyte growth factor HGF. In our study, the effect of VCAM-1 on HGF levels was investigated.
ECRS cell cultures were incubated with VCAM-1 and HGF levels were determined after 16, 24, 48 and 72 hours. RT-PCR was enrolled to depict the HGF-RNA levels.
Sixteen hours of incubation showed 28.5 pg/ml HGF, whereas in the control 16.3 pg/ml was detectable. After 24 and 36 hours, 37 pg/ml and 43.5 pg/ml HGF were measured in the incubated cell cultures, respectively; 72 hours of incubation with VCAM-1 resulted in 50.6 pg/ml HGF, whereas 23.5 pg/ml was determined in the controls. The RT-PCR for HGF also showed increased concentration in the incubated cells after 72 hours.
VCAM-1 induced an increase in levels of HGF in the ECRS cell cultures. The rising transcriptional activity was demonstrated by means of RT-PCR. The levels of HGF were within physiological ranges, suggesting that a misbalance between HGF and VCAM-1 resulted in the establishment of ECRS. Further experiments are necessary to reveal the role of HGF in the development of ECRS. This is the first report about the effect of VCAM-1 on growth factors in ECRS cell culture.
Full-text · Article · Jan 2008 · In vivo (Athens, Greece)
[Show abstract][Hide abstract] ABSTRACT: External auditory canal cholesteatoma (EACC) is a chronic inflammation of the bony ear meatus. Its etiology is not clearly understood. Other than surgical intervention, conservative methods are investigated for different cholesteatomas. Inducing apoptosis seems to be an appropriate strategy. Sulindac sulfone is a new class of targeted and pro-apoptotic drugs. It provokes apoptosis by inducing phosphorylation of beta-catenin, which is a multifunctional protein in the cell-cell adhesion complex.
EACC-cell cultures were incubated with different concentrations of sulindac sulfone (400 and 800 micromol). After 16, 24, and 48 h, beta-catenin concentrations were determined by ELISA, Western blot, and immunohistochemical analysis.
After 48 h incubation with 400 micromol sulindac sulfone, the average level of beta-catenin showed a decrease of 46% (0.004337 microg/mL) from those determined at 16 h with the same concentration of sulindac sulfone. At 800 micromol sulindac sulfone, the treated cell culture showed a reduction of 66.2% (0.003443 microg/mL). Comparing total protein content and the fraction of beta-catenin at different points in time, the concentration of beta-catenin decreased in both EACC cell cultures, 400 micromol (minus 63%) and 800 micromol (minus 81%).
The results presented in this paper are the first to demonstrate the chemopreventive effects of the agent sulindac sulfone on cholesteatomas. The greatest decrease of beta-catenin was observed between 16 and 24 h incubation. The inhibitory effect of sulindac sulfone as a local treatment seems to be a useful additional tool for nonsurgical approach to the therapy of EACCs.
No preview · Article · Jun 2007 · Archives of Medical Research