Dietmar Thurnher

Non-steroidal anti-inflammatory drugs induce apoptosis in head and neck cancer cell lines.

Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit tumorigenesis in colorectal cancer due to the induction of apoptosis. Disturbances of cellular pathways ultimately leading to apoptosis may contribute to the process of neoplastic transformation and immortalization. In this study we wanted to determine the influence of different NSAIDs (indomethacin, ibuprofen and sodium salicylate) and hydrocortisone on Bcl-2 expression and the apoptotic behavior of head and neck tumor cell lines and normal oral keratinocytes. Bcl-2 expression was determined by monoclonal antibody staining and fluorescence-activated cell-sorting measurement. Apoptotic cells were visualized with a epifluorescence microscope after staining with CytoDeath M30 antibody. Indomethacin (1 mM) and ibuprofen (1 mM) significantly reduced Bcl-2 expression in the cancer cell lines tested and might be thought responsible for the observed increase in apoptosis. At all concentrations tested the influence of sodium salicylate and hydrocortisone on Bcl-2 expression was not significant. In contrast, the NSAIDs tested had only a minor influence on normal oral keratinocytes. Our results demonstrate a significant reduction in growth and an increase in apoptosis, possibly due to a reduction in Bcl-2 expression. after exposure to indomethacin and ibuprofen in the head and neck cancer cell lines tested.Non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit tumorigenesis in colorectal cancer due to the induction of apoptosis. Disturbances of cellular pathways ultimately leading to apoptosis may contribute to the process of neoplastic transformation and immortalization. In this study we wanted to determine the influence of different NSAIDs (indomethacin, ibuprofen and sodium salicylate) and hydrocortisone on Bcl-2 expression and the apoptotic behavior of head and neck tumor cell lines and normal oral keratinocytes. Bcl-2 expression was determined by monoclonal antibody staining and fluorescence-activated cell-sorting measurement. Apoptotic cells were visualized with a epifluorescence microscope after staining with CytoDeath M30 antibody. Indomethacin (1 mM) and ibuprofen (1 mM) significantly reduced Bcl-2 expression in the cancer cell lines tested and might be thought responsible for the observed increase in apoptosis. At all concentrations tested the influence of sodium salicylate and hydrocortisone on Bcl-2 expression was not significant. In contrast, the NSAIDs tested had only a minor influence on normal oral keratinocytes. Our results demonstrate a significant reduction in growth and an increase in apoptosis, possibly due to a reduction in Bcl-2 expression, after exposure to indomethacin and ibuprofen in the head and neck cancer cell lines tested.

Differential Expression Pattern of Cyclooxygenase-1 and -2 in Head and Neck Squamous Cell Carcinoma

Objective—The enzyme cyclooxygenase catalyzes the first step of the synthesis of prostanoids. Cyclooxygenase has been shown to exist in two distinct isoforms: cyclooxygenase-1 is constitutively expressed as a housekeeping enzyme in most tissues whereas the inducible cyclooxygenase-2 has been reported to be involved in inflammatory processes and in the carcinogenesis of squamous cell carcinoma. The aim of this study was to investigate the distribution patterns of cyclooxygenase-1 and -2 in peritumoral lymphocytic infiltrates and tumor cells of head and neck carcinoma. Material and Methods—Immunohistochemical analysis was performed using paraffin-embedded tumor specimens from 24 patients suffering from oropharyngeal, hypopharyngeal and oral squamous cell carcinomas. Results—We observed that cyclooxygenase-2 immunoreactivity, compared to that of cyclooxygenase-1, was significantly increased in peritumoral lymphocytic infiltrates as well as in tumor cells. Conclusion—The expression of cyclooxygenase-2 in both tumor specimens and the surrounding peritumoral lymphocytic infiltrates supports the hypothesis that cyclooxygenase may be one of several important links between chronic inflammation and carcinogenesis.

Non-radioactive Semiquantitative Testing for Expression Levels of Telomerase Activity in Head and Neck Squamous Cell Carcinomas may be Indicative for Biological Tumour Behaviour

Head and neck cancer arises and progresses through specific genetic alterations which lead to an invasive immortal phenotype. The process of immortalization is associated with the activation of the enzyme telomerase, a ribonucleoprotein with reverse transcriptase activity which is capable of synthesizing telomeric repeats at the end of chromosomes. This enzyme is expressed in nearly all neoplasms and germline cells and is absent in most normal human somatic cells. Because of this expression pattern testing for telomerase activity may deliver useful diagnostic and/or prognostic information about clinical tumour behaviour. Telomerase activity was therefore analysed in 16 primary lesions of head and neck squamous cell carcinomas (HNSCC) using the polymerase chain reaction-based telomeric repeat amplification protocol (TRAP). For a sensitive semiquantitative analysis of telomerase activity TRAP products were mixed with Pico Green I and the fluorescence emission intensities were measured. All 16 samples tested positive. When the Pico Green I data were compared with clinical parameters, it was obvious that N0 necks revealed significantly (p < 0.05) lower emission intensities (i.e. telomerase activity) than N + necks. Our results indicate that a high telomerase activity in HNSCC may facilitate lymph node metastasis and that the estimation of telomerase activity is a useful diagnostic tool which could influence treatment modalities.

Reversible downregulation of telomerase activity by hyperthermia in osteosarcoma cells.

Telomerase, a ribonucleoprotein enzyme, maintains telomere length and is expressed by the majority of malignant tumours, but not in normal tissue. Telomerase facilitates the division of tumour cells and its activity has been suggested as a prognostic indicator, but so far the regulation or modulation of telomerase activity has not been described. Hyperthermia has been shown to decrease tumour growth by inhibition of proliferation. Therefore, the effect of hyperthermia on telomerase activity in human osteosarcoma cells was studied. Telomerase activity was measured by the Telomeric Repeat Amplification Protocol (TRAP) assay in three different osteosarcoma cell lines subjected to hyperthermia (42.5°C, 90min) and in controls cultured under basal conditions (37°C). Telomerase activity was strongly inhibited by hyperthermia and decreased in all cell lines tested after a recovery time of 2h under basal conditions (37°C) to an activity of 85%, after 12h 60% and with lowest activity 55% compared to activity of control cells. Telomearase activity then increased and reached the same, i.e. basal, level as before hyperthermia, after 112 h. These results show that hyperthermia results in a reversible downregulation of telomerase activity in osteosarcoma cells. This effect facilities studies on the regulation of telomerase activity and detailed information might lead to new therapeutic strategies.

Formveränderung und Trauma von Nase und Ohr Nasenpframidenfraktur

geschlossene oder offene Fraktur der Nasenbeine unter eventueller Mitbeteiligung des Nasenseptums isoliertes Vorkommen (haufig) oder in Kombination mit einer Mittelgesichtsfraktur direkte Gewalteinwirkung: Sportverletzung, Raufhandel etc.

Onkologie des Kopf- und Halsbereichs

Unter Kopf- und Halstumoren werden unterschiedliche kutane Malignome dieser Region und alle epithelialen Malignome von Lippe, Nasenhaupt- und Nebenhohlen, Mundhohle, des Pharynx (Oro-, Naso- und Hypopharynx) sowie des Larynx, der Speicheldrusen und der Schilddruse verstanden.

Die Entwicklung der Hals-Nasen-Ohren-Heilkunde im Wandel der Medizingeschichte

In den fruhen Hochkulturen war die Heilkunde von Religion und Magie gepragt. Ebenso stark war der Einfluss der Astrologie. Krankheiten wurden nicht selten als Strafe oder Prufung der Gotter angesehen. Mesolithische (15 000–6 000 v. Chr.) Felsenbilder in indischen Hohlen (Bhimbetka/Madhya Pradesch) werden als erste schriftliche Hinweise von medizinisch/chirurgischen Aktivitaten gedeutet. Die Urform des Arztestandes ent- wickelte sich ca. 3 000 v. Chr. im alten Indien und Agypten, wo bereits uber 700 Heilmittel bekannt waren. Insbesondere die Agypter erlangten durch das Einbalsamieren der Leichen basale anatomische und pathophysiologische Kenntnisse. So wurden beispielsweise im Ebers-Papyrus, der auf ca. 1500 v. Chr. datiert wird und dessen Ursprunge bis ins 3. Jht. v. Chr. zuruckreichen, die Herzfunktion und die Blutgefase beschrieben.