Teresa Steinbichler

The role of exosomes in cancer metastasis

Exosomes are small membrane vesicles with a size ranging from 40 to 100nm. They can serve as functional mediators in cell interaction leading to cancer metastasis. Metastasis is a complex multistep process of cancer cell invasion, survival in blood vessels, attachment to and colonization of the host organ. Exosomes influence every step of this cascade and can be targeted by oncological treatment. This review highlights the role of exosomes in the various steps of the metastatic cascade and how exosome dependent pathways can be targeted as therapeutic approach or used for liquid biopsies.

Tumor-associated fibroblast-conditioned medium induces CDDP resistance in HNSCC cells

Objective EMT (epithelial to mesenchymal transition) contributes to tumor progression and metastasis. We aimed to investigate the effects of EMT on CDDP resistance in HNSCC (head and neck squamous cell carcinoma)-cells. Methods EMT was induced using conditioned medium from a tumor cell/fibroblast co-culture. HNSCC cells were alternatively treated with TGF-β1. The response to CDDP was evaluated with viability and clonogenic assays. Results Treatment of SCC-25/Detroit 562 cells with conditioned medium increased viability of the tumor cells. Moreover, it doubled the IC50 of CDDP of SCC-25 cells from 6.2 μM to 13.1 μM (p < 0.001). The IC50 of CDDP of Detroit 562 cells was increased following treatment with conditioned medium from 13.1 μM to 26.8 μM (p < 0.01). Colony forming ability after treatment with 5 or 10 μM CDDP was significantly higher in HNSCC cells treated with co-culture conditioned medium than in controls (p < 0.05). Treatment with TGF-β1 had no effect on the IC50 of CDDP (p > 0.1). Conclusions Cell free medium from a co-culture was able to induce EMT in HNSCC cells. Co-culture treated HNSCC cells revealed increased viability and were less sensitive to CDDP treatment. TGF-β1 also induced a mesenchymal phenotype, but did not alter resistance to CDDP in HNSCC cells.

Microdebrider-assisted intracapsular Tonsillectomy in adults with chronic or recurrent tonsillitis

We compared the effectiveness and morbidity of microdebrider‐assisted total intracapsular tonsillectomy (ICTE) with conventional extracapsular tonsillectomy (ECTE) in adults with chronic or recurrent tonsillitis.

Chondrosarcoma of the nasal cavity in a patient with Maffucci syndrome: case report and review of the literature

IntroductionMaffucci syndrome is a rare, congenital, non-hereditary mesodermal dysplasia, manifested by multiple enchondromas and hemangiomas. Malignant transformation of these lesions is seen in up to 40% of the cases.Case reportWe present a case of a patient with Maffucci syndrome and an associated chondrosarcoma of the nose. Treatment consisted of surgical resection. Because of the low grade of the tumor, additional treatment, such as radiotherapy, was not necessary.ConclusionMaffucci syndrome is an exceedingly rare mesodermal dysplasia. Its manifestation in the head and neck region is even less common. Malignant transformation of the associated enchondromas is common, and should be considered whenever a change of the clinical course occurs. Random, periodically performed X-ray examinations give little additional information on malignant transformation and are considered useless.

Epithelial-mesenchymal crosstalk induces radioresistance in HNSCC cells

Objective Epithelial-mesenchymal crosstalk (EMC) contributes to tumor progression, chemoresistance and acquisition of a mesenchymal phenotype (EMT) of cancer cells. This study aims to investigate the effects of EMC on radioresistance in head and neck squamous cell carcinoma (HNSCC) cells. Methods In tumor cell lines, the response of HNSCC cells, stimulated with EMC conditioned medium (CM), to irradiation was evaluated with viability and clonogenic assays. Dose modifying factors (DMF) were calculated from the results of clonogenic assays. Potential pathways involved in radioresistance were analyzed with quantitative Real-Time PCR and western blot. Results CM significantly reduced the doubling time of SCC-25 cells (from 32.8 hours to 16.8 hours, p=0.0001) and Detroit 562 cells (from 88.5 hours to 29.6 hours, p=0.014). Further it increased clonogenic survival after irradiation. The DMF of CM was 2.04 ± 0.43 (mean ± standard deviation) for SCC-25 cells (p=0.015) and 2.14 ± 0.34 for Detroit 562 cells (p=0.008). Treatment with CM more than tripled the ERCC1 and survivin gene expression in SCC-25 cells. Conclusion EMC induced pathways involved in cell survival and DNA repair and led to increased radioresistance in HNSCC cells.

Photodynamic Effect of Methylene Blue and Low Level Laser Radiation in Head and Neck Squamous Cell Carcinoma Cell Lines

Photodynamic therapy (PDT) is suggested to have an impact on the treatment of early stage head and neck cancers (HNSCC). We investigated the effect of PDT with methylene blue (MB) and a diode laser (660 nm) as the laser source on HNSCC cell lines as an in vitro model of surface oral squamous cell carcinoma. Cell-cultures were exposed to 160 µM MB for 4 min and to laser light for 8 min. Viability was proven via cell viability assay and clonogenic survival via clone counting assay. The combination of MB and diode laser evidenced high efficient loss of cell viability by 5% of the control, while treatment with the same concentration of MB for 4 min alone showed a viability of 46% of the control. In both SCC-25 and Detroit 562 HNSCC cells, MB combined with the laser allowed a significant abrogation of clonogenic growth (p < 0.01), especially in the case of Detroit 562 cells less than 1% of the suspension plated cells were able to grow tumor cell nests. Multiresistant (Detroit 562) HNSCC cells expressing cancer stem cell markers are sensitive to MB/red laser combined PDT.

Separation of cell survival, growth, migration, and mesenchymal transdifferentiation effects of fibroblast secretome on tumor cells of head and neck squamous cell carcinoma:

Fibroblasts play a central role in tumor invasion, recurrence, and metastasis in head and neck squamous cell carcinoma. The aim of this study was to investigate the influence of tumor cell self-produced factors and paracrine fibroblast–secreted factors in comparison to indirect co-culture on cancer cell survival, growth, migration, and epithelial–mesenchymal transition using the cell lines SCC-25 and human gingival fibroblasts. Thereby, we particularly focused on the participation of the fibroblast-secreted transforming growth factor beta-1.Tumor cell self-produced factors were sufficient to ensure tumor cell survival and basic cell growth, but fibroblast-secreted paracrine factors significantly increased cell proliferation, migration, and epithelial–mesenchymal transition–related phenotype changes in tumor cells. Transforming growth factor beta-1 generated individually migrating disseminating tumor cell groups or single cells separated from the tumor cell nest, which were characterized by reduced E-cadherin expression. At the same time, transforming growth factor beta-1 inhibited tumor cell proliferation under serum-starved conditions. Neutralizing transforming growth factor beta antibody reduced the cell migration support of fibroblast-conditioned medium. Transforming growth factor beta-1 as a single factor was sufficient for generation of disseminating tumor cells from epithelial tumor cell nests, while other fibroblast paracrine factors supported tumor nest outgrowth. Different fibroblast-released factors might support tumor cell proliferation and invasion, as two separate effects.

Evaluation of a German version of the tonsil and adenoid health status instrument

BackgroundTo create and validate a German version of the Tonsil and Adenoid Health Status Instrument (TAHSI) for evaluation of tonsillectomy outcome in adult patients with chronic or recurrent tonsillitis.Subjects and methods46 healthy volunteers were assessed twice in a 6 week interval with the TAHSI questionnaire. Their results were compared with 45 patients suffering from chronic tonsillitis before tonsillectomy and 6 months following surgery. For internal consistency, Cronbach’s alpha was calculated; to identify normal score values, the optimum cutoff between healthy and diseased individuals was identified with receiver operating characteristic analysis; and responsiveness was assessed using Guyatt’s Responsiveness Index (GRI).ResultsCronbach’s alpha for all questions was 0.92. Test- retest intraclass correlation coefficient was 0.89 (95% confidence interval 0.80-0.94 p < 0.001). Mean score for the healthy individuals was 7.0 (95% confidence interval 4.2-9.7). The optimum cut off score between healthy and diseased was 20 with a sensitivity of 80% and a specificity of 90% to differentiate controls from tonsillectomy patients.ConclusionThe TAHSI performed well in this validation tests and is considered a favorable instrument to evaluate the effectiveness of tonsillectomy in adults with chronic or recurrent tonsillitis.

Prognostic value of tumor volume in patients with head and neck squamous cell carcinoma treated with primary surgery

Tumor volume in head and neck squamous cell carcinoma (HNSCC) was mainly measured in nonsurgically treated patients. We analyzed the influence of tumor volume on complete response (CR), overall survival (OS), and clear surgical margins also in primarily surgically treated patients.

Eine seltene Differenzialdiagnose von oralen Leukoplakien

Eine 55-jährige Patientin stellte sich in unserer Ambulanz vor und berichtete sich vor circa 5–6 Wochen in die Wange gebissen zu haben. Daraufhin haben sich lokal schmerzhafte Bläschen gebildet, die initial mit Mundspülungen und Antibiotika behandelt wurden. Trotz dieser Maßnahmen haben die Beschwerden zugenommen und es wurde eine Probe durch den niedergelassenen Facharzt entnommen. Die histologische Untersuchung zeigte polypoide Schleimhautfragmente mit hochgradiger Dysplasie, entsprechend einem Carcinoma in situ, weshalb die Patientin zur weiteren Therapie an uns überwiesen wurde. Ansonsten hatte die Patientin keine wesentlichen Vorerkrankungen, nur ein Nikotinabusus von circa 20 Packyears war bekannt.