Publications (6)17.05 Total impact
- [Show abstract] [Hide abstract] ABSTRACT: To evaluate the efficacy and safety of a phytotherapeutic nasal spray containing Cyclamen europaeum (CE) in the treatment of acute rhinosinusitis (ARS). We performed a randomized, double-blind, placebo-controlled trial of CE nasal spray once daily for 15 days in 99 adult patients with moderate-to-severe ARS who also received amoxicillin 500 mg three times daily for the first 8 days. The primary endpoint was the change in mean total symptom scores (TSS) on day 7. Secondary endpoints included individual symptom scores (nasal congestion, mucus secretion, facial pain, impairment of smell) and endoscopic findings on days 7 and 15 and others. No statistically significant difference in TSS was noted for CE versus placebo on day 7. Moreover, the individual scores were not statistically different between the groups for the ITT-population on day 7. However, both a reduction in facial pain and an improvement in endoscopically-assessed mucosal obstruction significantly favoured CE on day 7. The most common adverse events were nasal burning and mild epistaxis, but no severe adverse events were documented. In summary, this is the first randomized controlled trial on phytotherapy in patients with moderate-to-severe ARS demonstrating clinical safety and some encouraging effects of CE which merit to investigate phytotherapeutic products in further large-scale clinical trials.
- [Show abstract] [Hide abstract] ABSTRACT: Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy. The development of new treatment modalities in order to improve long-term survival of patients with HNSCC is imperative. Numerous studies have demonstrated that carcinogenesis and tumor cell dissemination is influenced by the tumor microenvironment. The protein-kinase-receptors (PTKs) are essential elements of the intracellular signal transduction pathway and regulate cell growth, development and apoptosis. Cell proliferation, migration, induction of tumor vascularization and carcinogenesis, invasion is regulated by a variety of angiogenic factors, such as PDGF (platelet-derived growth factor), VEGF (vascular endothelial growth factor) and their respective tyrosine kinase receptors (PDGF-R and VEGF-R). They present promising targets for anti-cancer therapy through abrogation of impaired signaling pathways. Indeed, imatinib, a small molecule drug targeting these protein kinases, has antiproliferative effects in several cancer types. The purpose of this study was to investigate the potential synergism of imatinib and carboplatin on the expression of PDGF, PDGF-R α/ß and VEGF in different HNSCC cell lines. Several tumor cell lines were subjected to increasing concentrations of carboplatin (3 and 7.5 µmol/l) and imatinib (18 and 30 µmol/l) and ELISA, immunohistochemical methods and RQ-PRC after 48, 72, 120 and 240 h were used to assess their expression levels. While PDGF-Rα/ß expression was unimpaired at lower imatinib concentrations (18 µmol/l), PDGF-Rα/ß expression was suppressed at 30 µmol/l, and suppression was enhanced by the presence of carboplatin. By RQ-PCR, a significant reduction of PDGF-Rα/ß expression was detected (p<0.5). We observed explicit significant reduction in VEGF levels with increasing concentrations of imatinib and with the combination of the two chemotherapeutic drugs (p<0.5). We report for the first time evidence of synergism of imatinib and carboplatin in suppressing VEGF, PDGF and PDGF-Rα/ß expression in HNSCC.
- [Show abstract] [Hide abstract] ABSTRACT: Squamous cell carcinoma of the head and neck (HNSCC) is the most common neoplasm arising in the upper aerodigestive tract. Unfortunately, the survival for this type of cancer has not improved significantly in the past 25 years. To enhance the survival rate multimodal therapy regimens have been set up. In these regimens chemotherapy plays a pivotal role in the majority of advanced cases. Transmembrane protein- tyrosine kinases (PTK) are fundamental elements of the signal transduction. In consequence, they might be promising targets for cancer therapy. Imatinib (STI 571) was originally designed to inhibit the BCR-ABL tyrosine kinase in chronic myeloid leukemia. But imatinib also has an inhibitory impact on the PTK receptor c-kit and on its PTK activity. Furthermore, growth and invasion of HNSCC are strongly influenced by the extracellular matrix (ECM). The ECM is altered by matrix metalloproteinases (MMP). In this study, we incubated different HNSCC cell lines with rising concentrations of imatinib and/or carboplatin. After an incubation time of up to 10 days, we evaluated c-kit, MMP-2 and MMP-14 by ELISA techniques and immunohistochemical methods. Especially the combination of 7.5 μmol carboplatin with 30 μmol imatinib resulted in a significant decrease in MMP-2 expression in all observed cell lines (p<0.05). We did not demonstrate a significant alteration in c-kit expression by imatinib and carboplatin. We observed an increase in apoptosis in HNSCC cells by the combination of the two observed chemotherapeutic drugs. In all cell lines tested, expression of c-kit and MMP could be demonstrated. Our results indicate that MMP-2 expression was suppressed in the presence of imatinib. Thus, imatinib may exert in part its inhibitory effect on malignant cell growth via the blockage of the signal transduction of PTK receptors. Further studies are warranted, especially one keeping in mind the moderate toxicity of imatinib.
- [Show abstract] [Hide abstract] ABSTRACT: Squamous cell carcinoma of the head and neck (SCCHN) presents at a locally advanced (LA) stage in many patients. Chemotherapy, which is one fundamental therapy mode for local disease control of inoperable disease or if organ preservation is desired, has become an important factor of first line treatment regimens either during or prior to radiotherapy (RT). Patients with locoregionally advanced inoperable, recurrent or metastatic disease still have a poor prognosis, which enforces the need for new treatment approaches and new drug therapies, adjusted to the different settings of the disease. One innovative progress for this collective of patients with locally advanced tumor was the implementation of Docetaxel in chemotherapeutic regimes in optimal combination with concurrent chemoradiotherapy or in neoadjuvant setting of induction phase treatment. Docetaxel combined with the conventional chemotherapy regimen, containing Cisplatin and 5-Fluorouracil (TPF), is now acknowledged as being the gold standard of induction treatment. Various studies suggest survival advantage due to the induction chemotherapy (ICT) followed by chemoradiotherapy, which is known as sequential therapy, over chemoradiotherapy alone. In contrast to prevailing studies we administered Docetaxel, Carboplatin and 5-FU within the frame-work of induction chemotherapy instead of conventional use of Cisplatin for five patients with locoregionally advanced HNSCC. The clinical progress was evaluated through cross section imaging (computer tomography/MRI) prior and after ICT and classified following the RECIST criteria. Due to a very small collective of patient and the administration of Carboplatin instead of Cisplatin in this study, it was not possible to document the the efficacy of ICT (TPF) concerning survival advantage in patient with locoregionally advanced head and neck tumors. Further studies with an extended collective of patients are neccessary.
- [Show abstract] [Hide abstract] ABSTRACT: To provide an overview of clinical parameters generally used for monitoring the clinical efficacy of specific immunotherapy (SIT) in clinical trials. In particular, it focuses on primary and secondary outcome measurements and reviews the advantages and disadvantages of each method. In 2007, the World Allergy Organization defined the severity of symptoms and the need for concomitant medication as primary endpoint parameters in clinical outcome measures of SIT. Furthermore, it was stated that the symptom score should always be combined with the rescue medication score. The 'quality of life' is usually used as a secondary outcome measure in clinical trials on SIT. In clinical trials on SIT, several clinical parameters are commonly used to provide evidence of the clinical efficacy of the therapy. These parameters should include a measurement of symptoms and of the use of concomitant medications, which represent the 'primary outcome' parameters. Both physician-rated and patient self-rate scores have been implemented in clinical studies. Furthermore, disease-unspecific (generic) and disease-specific questionnaires for evaluating the quality of life are widely used and partially validated as 'secondary outcome' parameters. This review provides an overview on the different methods to measure the clinical outcome of SIT and points out the advantages and disadvantages of each method.
- [Show abstract] [Hide abstract] ABSTRACT: The external auditory canal cholesteatoma (EACC) is a rare disease with hyperproliferation and destructive growth in the adjacent structures. Down-regulation of beta-catenin (key component of the zonula adherens) is a pivotal factor for loose tissue integrity and invasiveness. Transforming growth factor beta1 (TGF-beta1) was reported to decrease beta-catenin in mammary epithelium. We investigated the abrogation of TGF-beta1 and beta-catenin expression in EACC culture cells. Cultured EACC-specimens were incubated with 6 micromol TGF-beta1 antisense. After 48 h, expression of beta-catenin was determined by means of immunohistochemistry. The cells showed an increased mural reactivity to beta-catenin, and intracellular reactivity was unchanged. The untreated cells showed a loss of beta-catenin expression at the membranes. The predominant membranous location after treatment with TGF-beta1 antisense suggests increased tendency of the cells for tissue formation and strong cell-cell adhesion rather than migratory and invasive character, and thus TGF-beta1 antisense application is a useful therapeutical strategy.
Universität MannheimMannheim, Baden-Württemberg, Germany