The bFGF and VEGF mRNA expression and the bFGF and VEGF protein expression in sporadic VS correlates to the tumour volume, to the tumor growth index, and to the MVD. This might indicate an angiogenic and neurotrophic influence of these factors and a possible involvement in the growth of sporadic VS.
Promoter hypermethylation of tumor suppressor genes (TSGs) is a common feature of primary cancer cells. However, to date the somatic epigenetic events that occur in head and neck squamous cell carcinoma (HNSCC) tumorigenesis have not been well-defined. In the present study, we analyzed the promoter methylation status of the genes mutL homolog 1 (MLH1), Ras-association domain family member 1 (RASSF1A) and O-6-methylguanine-DNA methyltransferase (MGMT) in 23 HNSCC samples, three control tissues and one HNSCC cell line (UM-SCC 33) using methylation-specific PCR (MSP). The expression of the three proteins was quantified by semi-quantitative immunohistochemical analysis. The cell line was treated with the demethylating agent 5-azacytidine (5-Aza) and the methylation status after 5-Aza treatment was analyzed by MSP and DNA sequencing. Proliferation was determined by Alamar blue staining. We found that the MGMT promoter in 57% of the analyzed primary tumor samples and in the cell line was hypermethylated. The MLH promoter was found to be methylated in one out of 23 (4%) tumor samples while in the examined cell line the MLH promoter was unmethylated. The RASSF1A promoter showed methylation in 13% of the tumor samples and in the cell line. MGMT expression in the group of tumor samples with a hypermethylated promoter was statistically significantly lower compared to the group of tumors with no measured hypermethylation of the MGMT promoter. After treatment of the cell line with the demethylating agent 5-Aza no demethylation of the methylated MGMT and RASSF1A genes were determined by MSP. DNA sequencing verified the MSP results, however, increased numbers of unmethylated CpG islands in the promoter region of MGMT and RASSF1A were observed. Proliferation was significantly (p<0.05) reduced after treatment with 5-Aza. In summary, we have shown promoter hypermethylation of the tumor suppressor genes MGMT and RASSF1A in HNSCC, suggesting that this epigenetic inactivation of TSGs may play a role in the development of HNSCC. 5-Aza application resulted in partial demethylation of the MGMT and RASSF1A TSGs and reduced proliferation of the tumor cells suggesting further evaluation of 5-Aza for HNSCC treatment.
The aim of the study is to present the results of combination treatment for adult non-traumatic subglottic stenosis (SGS). This is a retrospective chart review of 12 female patients (age range 32-76 years) with idiopathic SGS (eight patients) and Wegener's granulomatosis. All patients had a hard and 11 a short (less than 1 cm) stenosis. Eleven patients were treated with endoscopic CO(2) laser, one with Nd-YAG laser. Topical triamcinolone was applied to all. In 10 patients, topical mitomycin C (MMC) was additionally applied. Symptom severity and airway resistance (AR) were evaluated pre- and post-interventionally. Postoperatively, oral steroids (and/or methotrexate) and proton pump inhibitors (PPI) were prescribed. Follow-up period ranged between 7 and 115 months. All patients reported a significant improvement in obstructive symptoms. Average AR preoperatively was 1.004 kPa/(L/s) and postoperatively 0.526 kPa/(L/s). Three patients underwent surgery once, 2 required a second surgery, 5 were operated 3 times, one 5 times, and one 7 times. The latter two patients had not received local MMC treatment. Endoscopic laser surgery combined with local MMC and triamcinolone application and postoperative oral steroid/methotrexate and PPI therapy provides a treatment option that results in prolongation of the symptom-free time intervals and avoidance of open surgery in patients with idiopathic and Wegener-associated hard and short SGS.
The retrosigmoid (suboccipital) approach is one of four surgical approaches for the treatment of vestibular schwannomas (acoustic neuromas). It is increasingly used by otologic surgeons, and in experienced hands is associated with improved results and more limited complications. Mortality rates are minimal and often zero, while postoperative sequelae, on the other hand, are not rare. In order to not only save the patient's life, but also to assure good quality of life after the surgery, one must consider many different aspects of management of the respective complications. In this review the issues of current management of CSF leak and meningitis, facial paresis, headache, hearing loss, unsteadiness, disequilibrium, vertigo, tinnitus, cerebellar and brain stem injuries or abscess, vascular complications and venous air embolism after retrosigmoid approach for removal of vestibular schwannomas are presented.
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