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2.
Infection ; 51(2): 489-495, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36178603

ABSTRACT

PURPOSE: Raising awareness of respiratory diphtheria and for the importance of early antitoxin administration. METHODS: Report of a case of fulminant, imported respiratory diphtheria in an otherwise healthy 24-year-old Afghan refugee in Austria in May 2022. RESULT: This was the first case of respiratory diphtheria in Austria since 1993. Diphtheria antitoxin was administered at an already progressed disease stage. This delay contributed to a fulminant disease course with multiorgan failure and death. CONCLUSION: In high-income countries with low case numbers, awareness of respiratory diphtheria and for the importance of early antitoxin administration must be raised.


Subject(s)
Corynebacterium diphtheriae , Diphtheria , Refugees , Humans , Young Adult , Adult , Diphtheria/diagnosis , Diphtheria/drug therapy , Austria , Diphtheria Antitoxin
3.
Cancer Invest ; 24(3): 242-5, 2006.
Article in English | MEDLINE | ID: mdl-16809151

ABSTRACT

BACKGROUND: The purpose of this retrospective evaluation was to assess the palliative effect of oral etoposide in heavily pretreated patients with squamous cell carcinoma of the head and neck. PATIENTS AND METHODS: Between October 1995 and February 2003, a total of 26 patients with metastatic and/or recurrent squamous cell carcinoma of the head and neck (SCCHN) were treated with oral etoposide. Therapy consisted of etoposide at a total dose of 100 mg daily for 7 days and was repeated every 4 weeks until progression of disease or for a maximum of 8 courses. Eighteen patients underwent primary surgery of the tumour followed by adjuvant irradiation or surgery after neoadjuvant radiochemotherapy. Eight patients had primary irradiation with or without concomitant chemotherapy. All patients previously received at least one palliative chemotherapy with cisplatin/5-floururacil (5-FU) or cisplatin/taxotere. Patients did not routinely receive anti-emetic medication. RESULTS: All patients were eligible for toxicity and survival assessment, and 24 of 26 patients for response evaluation according to an intention-to-treat principle. Two patients had a partial response (8 percent); disease was stable in 9 patients (35 percent) and progressed in 13 patients (50 percent). The median time to progression for all patients was 3 months (range, 2-54), and median overall survival was 10 months (range, 2-52). Toxicity was in general mild and moderate (Grade 1 and 2), except three patients, who experienced Grade 3 anaemia, and one patient who had Grade 3 thrombocytopenia without bleeding complications. Severe nonhematologic adverse reactions were not seen, except for alopecia. CONCLUSION: Our data suggest that oral etoposid is markedly effective, in regard to stabilization of disease and survival, and an excellent tolerated therapy for pretreated patients with recurrent and/or metastatic head and neck carcinomas. Its advantage over other commonly used and more intensive regimens such as 5-fluorouracil (5-FU) + cisplatin or taxane-containing combinations is its superior tolerance, in particular the incidence of nausea and vomiting, complete alopecia, and/or hematologic complications.


Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Etoposide/therapeutic use , Head and Neck Neoplasms/drug therapy , Administration, Oral , Aged , Female , Humans , Male , Middle Aged , Neoplasm Metastasis/drug therapy , Neoplasm Recurrence, Local/drug therapy , Salvage Therapy , Treatment Outcome
4.
Br J Anaesth ; 96(5): 650-9, 2006 May.
Article in English | MEDLINE | ID: mdl-16574723

ABSTRACT

BACKGROUND: Superimposed high-frequency jet ventilation (SHFJV), which does not require any tracheal tubes or catheters, was developed specifically for use in laryngotracheal surgery. SHFJV uses two jet streams with different frequencies simultaneously and is applied in the supraglottic space using a jet laryngoscope and jet ventilator. METHODS: Between 1990 and 2004, SHFJV was studied in 1515 consecutive patients (including 158 children requiring laryngotracheal surgery) prospectively. Ventilation was performed with an air/oxygen mixture and anaesthesia was administered i.v. RESULTS: Adequate oxygenation and ventilation was achieved in 1512 patients. Arterial blood gas analyses (BGA) were performed between 1990 and 1994; thereafter BGA was only performed in patients with high-grade stenosis of the larynx/trachea or high-risk patients [n=623, mean Pa(O(2)) 133.8 (39.4) mm Hg and mean Pa(CO(2)) 42.3 (10.1) mm Hg]. There were no significant changes in Pa(O(2)) or Pa(CO(2)) during the entire period of SHFJV. No complications secondary to the ventilation technique were observed; in particular, no barotrauma occurred. Three patients required tracheal intubation. SHFJV was also successfully used for laser surgery (n=312). It proved to be a safe mode of ventilation without any complications such as airway fire, major haemorrhage, or aspiration of debris. CONCLUSION: SHFJV is an advanced ventilation mode playing a pivotal role in the (open) ventilatory support/ventilation of patients with laryngotracheal stenosis. It is particularly indicated in cases of severe stenosis and offers optimal conditions for laryngotracheal surgery, including laser surgery and stent implantation techniques.


Subject(s)
High-Frequency Jet Ventilation/methods , Laryngostenosis/surgery , Tracheal Stenosis/surgery , Adult , Aged , Carbon Dioxide/blood , Female , Humans , Laryngoscopes , Laryngoscopy , Laser Therapy , Male , Middle Aged , Oxygen/blood , Partial Pressure , Prospective Studies
5.
Acta Neurochir (Wien) ; 144(12): 1255-64; discussion 1264, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12478336

ABSTRACT

BACKGROUND: The authors retrospectively compared the results of three different treatment modalities (surgery, conventional radiotherapy and gamma knife radiosurgery) in patients with paragangliomas of the temporal bone, in order to determine the optimal current treatment concept. METHOD: Between 1978 and August 2001, 53 patients (12 men and 41 women; mean age, 58.3 years; range, 17 to 84 years) with paragangliomas of the temporal bone were treated at the neurosurgery and ENT departments of the University of Vienna. According to the Fisch classification, 6 patients had class B tumours, 20 had class C, and 27 patients had class D tumours. Thirty-two patients (mean age, 57.0 years; 6 B, 14 C, 12 D) underwent surgery. In 17 cases the tumour was embolised prior to surgery. Nine patients (mean age, 73.9 years; 6 C, 3 D) received primary radiotherapy (median total dose, 46.8 Gy). Six patients (mean age, 73.5 years; 6 D) underwent primary radiosurgery (median centre dose 24, Gy) and 6 patients (6 D) admitted from other departments with recurrent tumours adjuvant radiosurgery (median centre dose, 25.5 Gy). FINDINGS: In 20 of the surgical cases (62.5%) complete tumour resection was achieved and the patients required no further treatment over a mean follow-up period of 9.1 years. Of the 12 patients with incomplete tumour resection, 9 (5 C, 4 D) received postoperative adjuvant radiotherapy and three patients (3 D) adjuvant radiosurgery. In 15 (83.4%) of the 18 patients who underwent radiotherapy the tumours showed no signs of progression and the patients remained clinically unchanged over a mean period of 9.4 years. Three patients (16,6%) experienced progression of their tumour within an average period of 2.8 years. In the 15 patients who underwent primary radiosurgery, an objective 100% tumour control rate with no evidence of progression of disease was observed. INTERPRETATION: The results indicate that the most effective current treatment option for patients with paragangliomas of the temporal bone is a single-stage radical tumour resection, performed in advanced tumours as an interdisciplinary neuro-otosurgical procedure. For subtotally resected or non-resectable tumours, gamma knife radiosurgery has proved to be a safe and effective treatment modality.


Subject(s)
Outcome Assessment, Health Care , Paraganglioma/radiotherapy , Paraganglioma/surgery , Radiosurgery , Skull Neoplasms/radiotherapy , Skull Neoplasms/surgery , Temporal Bone/radiation effects , Temporal Bone/surgery , Adolescent , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Paraganglioma/pathology , Radiotherapy, Adjuvant , Retrospective Studies , Skull Neoplasms/pathology , Temporal Bone/pathology , Time Factors
6.
Oncology ; 63(2): 145-50, 2002.
Article in English | MEDLINE | ID: mdl-12239449

ABSTRACT

PURPOSE: Since the combination of cisplatin and docetaxel have demonstrated activity in squamous cell carcinomas of the lung and oesophagus before, promising results in recurrent metastatic head and neck cancer were expected. PATIENTS AND METHODS: Between September 1998 and October 2000, 40 patients entered this trial, 38 of whom were evaluable. Six patients were previously untreated, 24 had surgery and/or radiotherapy and 13 had received chemoradiation and/or surgery. Therapy consisted of 75 mg/m(2) docetaxel (1-hour infusion) and 75 mg/m(2) cisplatin (90-min infusion) on day 1, repeated every three weeks for a maximum of 6 courses. All patients received corticosteroids routinely, 5-HT3-antagonists, and hydration. RESULTS: The overall response rate was 52.5% (95% confidence interval, 36.1 to 68.5%) including 7 complete (17.5% complete response; CR) and 14 partial remissions (35% partial response; PR). The overall response rate in patients who had no prior treatment (n = 6) was 100%, including 3 CR and 3 PR. In patients who had prior surgery and/or radiotherapy (n = 21) an overall response rate of 42.8% was observed, including 2 CR and 7 PR; 8 patients (38.1%) had stable disease, while disease progressed in 3 (14.3%). Six of 13 patients (46.2%) who had prior chemoradiation +/- surgery responded, including 2 CR (15.4%) and 4 PR (30.8%), no change was seen in 4 patients (30.8%) and tumour progressed in 2 (15.4%). The median response duration for all patients was 10 months (range, 3-20), the median overall survival was 11 months (range, 1-30). Myelosuppression was commonly observed; WHO grade 3 or 4 neutropenia occurred in 12 patients (30%) each, and was complicated by septicaemia in 5 cases. WHO grade 3 anaemia was observed in only 3 patients (7.5%). Severe non-hematologic toxicity except for alopecia was rarely observed, and included diarrhea in 2 (5%), nausea/vomiting in 2 patients (5%) and stomatitis in 1 patient (2.5%). CONCLUSION: Our data suggest that docetaxel and cisplatin in combination is an effective and fairly well tolerated regimen for the treatment of head and neck cancer with an excellent response rate in previously untreated patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Paclitaxel/analogs & derivatives , Taxoids , Adult , Aged , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/secondary , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Disease-Free Survival , Docetaxel , Head and Neck Neoplasms/mortality , Humans , Middle Aged , Neoplasm Metastasis , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Palliative Care , Recurrence , Survival Rate , Time Factors
7.
Laryngorhinootologie ; 81(8): 568-72, 2002 Aug.
Article in German | MEDLINE | ID: mdl-12189573

ABSTRACT

A rare case of adenosquamous carcinoma in a 74 year-old man is reported. Presenting as a nodule on the soft palate, diagnosis was prolonged because of the benign macroscopic aspect. CT-scan and MR-tomography showed an encapsulated lesion but biopsy and histologic examination revealed the typical features of adenosquamous carcinoma. The tumour consisted of adenocarcinoma and squamous cell carcinoma in close proximity to minor salivary glands of which the tumour seemed to have its origin. This entity, although rare in the head and neck region has been documented to be very aggressive with early regional and hematogenic metastasis. Therefore it has to be distinguished from other tumours, especially from mucoepidermoid carcinomas of the salivary glands, which have a better prognosis. Adenosquamous carcinoma is considered to have poor radiosensitivity and chemotherapeutic approaches have also not been successful in the literature. In our case radical surgical therapy was performed by excision of the whole soft palate and bilateral neck dissection. This resulted in total removal of the tumour but revealed bilateral lymph node metastases. Vital functions were saved by reconstruction of the palate with a free vascularized tensor-fasciae-latae-perforator-flap. For the first time in a case of adenosquamous carcinoma carcinoembryonic antigen in serum was monitored. A pretherapeutical 29-fold elevation resulted in a marked decrease after surgery, but supranormal values indicated remaining tumour burden which was found in metastases in the lung. Because of the limitations in therapy, early histologic diagnosis is most important in this highly malignant tumour.


Subject(s)
Carcinoma, Adenosquamous , Palatal Neoplasms , Aged , Biopsy , Carcinoembryonic Antigen/analysis , Carcinoma, Adenosquamous/diagnosis , Carcinoma, Adenosquamous/diagnostic imaging , Carcinoma, Adenosquamous/pathology , Carcinoma, Adenosquamous/surgery , Diagnosis, Differential , Follow-Up Studies , Humans , Lung Neoplasms/secondary , Lymphatic Metastasis , Magnetic Resonance Imaging , Male , Palatal Neoplasms/diagnosis , Palatal Neoplasms/diagnostic imaging , Palatal Neoplasms/pathology , Palatal Neoplasms/surgery , Palate, Soft/pathology , Prognosis , Surgical Flaps , Time Factors , Tomography, X-Ray Computed , Treatment Outcome
8.
Alcohol Clin Exp Res ; 25(4): 496-501, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11329487

ABSTRACT

BACKGROUND: Alcohol increases the risk of cancers of the upper aerodigestive tract, but the biological mechanisms of this ethanol effect are still unclear. We recently reported that ethanol is able to induce in vitro proliferation accompanied by an increased number of cells in the S phase of the cell cycle in squamous cell carcinoma cell lines of the head and neck (SCCHN). In the current study we investigated the influence of ethanol over a limited period of time (96 hr) on cell cycle-regulating proteins involved in G1/S phase transition. METHODS: Synchronized cells of SCCHN cell lines JPPA (larynx) and SCC 9 and SCC 25 (tongue), as well as HaCaT (human immortalized keratinocytes)-used as a control-were cultured for 96 hr in the presence or absence of ethanol (10-3M). At several time intervals the expression of cyclin D1 and p21 and the phosphorylation status of the retinoblastoma protein (pRb) were determined by Western or Northern Blot analysis, or both. RESULTS: Ethanol had no influence on the protein expression of cyclin D1. In contrast, a distinct downregulation of p21 at the protein as well as the mRNA level could be detected. Furthermore, as a downstream event, the hyperphosphorylated form of the pRb increased. CONCLUSIONS: In the acute alcohol in vitro experiments, the marked downregulation of the important cell cycle inhibitor p21 and the corresponding increase of hyperphosphorylated pRb accelerate the progression of cells from the G1 to the S phase in the cell cycle. The importance of these data and their relevance to in vivo conditions remain speculative, but it could be a critical step in the multistep process of SCCHN carcinogenesis induced by ethanol.


Subject(s)
Carcinoma, Squamous Cell/metabolism , Central Nervous System Depressants/pharmacology , Ethanol/pharmacology , Head and Neck Neoplasms/metabolism , Retinoblastoma Protein/drug effects , rho GTP-Binding Proteins/drug effects , Humans , Keratinocytes/drug effects , Keratinocytes/metabolism , Phosphorylation , RNA, Messenger/drug effects , RNA, Messenger/metabolism , Retinoblastoma Protein/metabolism , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/metabolism , rho GTP-Binding Proteins/metabolism
9.
Anticancer Drugs ; 12(3): 205-8, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11290867

ABSTRACT

A phase II study was performed to assess the safety and efficacy of ifosfamide and mitoxantrone in recurrent and/or metastatic squamous cell carcinomas of the head and neck. Treatment consisted of ifosfamide 1500 mg/m2 in 1000 ml saline, infused over 60 min and mesna 20% of the total dose of ifosfamide in three doses for 3 days combined with mitoxantrone 12 mg/m2 given as a short infusion on day 1. Treatment courses were repeated every 4 weeks until a total of six cycles. Twenty-two patients entered this trial, 13 of whom had received chemo- and radiation therapy, and nine patients who underwent radiation therapy with or without prior surgery. We observed no objective response, with the exception of two patients who experienced minor response (reduction of tumor size of 25%). The dose-limiting toxicity was myelosuppression with grade 3/4 leukocytopenia in seven patients (32%) and grade 3/4 neutropenia in 15 (68%). Severe organ toxicity except alopecia (91%) was not observed. Ifosfamide combined with mitoxantrone does not improve the therapeutic armentarium in recurrent squamous cell carcinoma of the head and neck.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , DNA Topoisomerases, Type II , Head and Neck Neoplasms/drug therapy , Adult , Aged , Anemia/chemically induced , Antigens, Neoplasm , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/adverse effects , DNA-Binding Proteins , Diarrhea/chemically induced , Female , Follow-Up Studies , Humans , Ifosfamide/administration & dosage , Ifosfamide/adverse effects , Isoenzymes/antagonists & inhibitors , Male , Middle Aged , Mitoxantrone/administration & dosage , Mitoxantrone/adverse effects , Nausea/chemically induced , Neoplasm Metastasis , Neoplasm Recurrence, Local , Neutropenia/chemically induced , Stomatitis/chemically induced , Topoisomerase II Inhibitors , Treatment Outcome , Vomiting/chemically induced
10.
Acta Otolaryngol ; 121(1): 103-9, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11270487

ABSTRACT

The biologically active form of vitamin D3, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], inhibits proliferation and induces differentiation for various malignant cells, including squamous cell carcinoma cell lines of the head and neck (SCCHN). These effects are due to an arrest of cells in the G0/G1 phase of the cell cycle and are predominantly mediated by the vitamin D receptor. To further explore the molecular mechanisms of the antiproliferative activity in SCCHN we studied the influence of 1,25(OH)2D3 on the expression of the G1 phase-regulating proteins cyclin D1, p21 and p27. Furthermore, as a direct target of G1 protein complexes, we investigated the phosphorylation status of the retinoblastoma protein (pRb). Synchronized cells of 2 SCCHN cell lines [JPPA (laryngeal carcinoma) and SCC 9 (tongue carcinoma)] and human immortalized keratinocytes (HaCaT) were cultured for 96 h in the presence or absence (ethanol as control) of 1,25(OH)2D3 (10(-7) M). At various time intervals the cell cycle status was detected by fluorescence-activated cell sorting (FACS) analysis and in parallel the expression of cell cycle-regulating proteins was determined at the protein and mRNA levels. In all cell lines tested 1,25(OH)2D3 caused an arrest of cells in the G0/G1 phase of the cell cycle and markedly induced the expression of the inhibitors p21 and p27. No influence was detectable on the expression of cyclin D1. Induction of p21 and p27 mRNA revealed transcriptional regulation by the vitamin D receptor. Simultaneously, hyperphosphorylated pRb was transformed to the hypophosphorylated form. Our results demonstrate that the biologically active form of vitamin D3 directly regulates the expression of p21 and p27, inducing a G0/G1 phase arrest: one mechanism by which 1,25(OH)2D3 controls cell proliferation inSCCHN.


Subject(s)
Calcitriol/pharmacology , Carcinoma, Squamous Cell/genetics , Cell Cycle Proteins , Cell Cycle/drug effects , Cyclins/metabolism , Head and Neck Neoplasms/genetics , Microtubule-Associated Proteins/metabolism , Tumor Suppressor Proteins , Cell Line , Cyclin-Dependent Kinase Inhibitor p21 , Cyclin-Dependent Kinase Inhibitor p27 , Cyclins/genetics , Flow Cytometry , Humans , Immunoblotting , Microtubule-Associated Proteins/genetics , Polymerase Chain Reaction , RNA/analysis , Retinoblastoma Protein/analysis , Tumor Cells, Cultured
11.
J Oral Pathol Med ; 30(2): 91-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11168853

ABSTRACT

Autologous jejunal grafts used for primary reconstruction in cases of extensive soft tissue defects following tumor resection in the upper aerodigestive tract were investigated by immunohistochemistry (APAAP technique). Biopsies from eight patients were taken intra-operatively, at the time of transplantation and 2, 4, and 6 months post-operatively. A panel of monoclonal antibodies directed against surface antigens of the major subpopulations of the immune system was used. In all of the patients, a remarkable increase of all antigens investigated was detected 2 months post-operatively, which remained unchanged in the following biopsies (4 and 6 months postoperatively). Significantly higher numbers of CD45RA+ and CD45RO+ (P<0.05) leukocytes were detectable. This increase was due to both subsets of T and B cells, but only for CD19+ B cells was the increase significant. In addition, NK cells (CD16+ lymphocytic cells, P<0.01) and mature macrophages (25F9+ cells, P<0.01) increased. The first post-operative biopsy showed a significantly higher expression of activation-associated antigens (ICAM-1, VCAM, and HLA-DR) on monocytes/macrophages and endothelial cells. Our findings indicate that autologous jejunal grafts facilitate immunological function in the new microenvironment.


Subject(s)
B-Lymphocytes/pathology , Jejunum/transplantation , Mouth Neoplasms/surgery , Oropharyngeal Neoplasms/surgery , T-Lymphocytes/pathology , Aged , Antibodies, Monoclonal , Antigens, Surface/analysis , B-Lymphocyte Subsets/pathology , Biopsy , Endothelium, Vascular/pathology , Female , Follow-Up Studies , Granulocytes/pathology , HLA-DR Antigens/analysis , Humans , Intercellular Adhesion Molecule-1/analysis , Intraoperative Care , Jejunum/pathology , Killer Cells, Natural/pathology , Macrophages/pathology , Male , Middle Aged , Monocytes/pathology , T-Lymphocyte Subsets/pathology , Transplantation, Autologous , Vascular Cell Adhesion Molecule-1/analysis
12.
Head Neck ; 23(12): 1049-55, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11774390

ABSTRACT

BACKGROUND: Antiproliferative effects in neoplastic cells of different origin have been attributed to non-steroidal anti-inflammatory Drugs (NSAIDs) during the past few decades. METHODS: We tested the influence of NSAIDs and hydrocortisone on cell lines derived from head and neck squamous cell cancer (HNSCC) and on normal oral mucosal keratinocytes. Cell numbers were assayed by cell counting, proliferation, telomerase activity with a colorimetric assay, and cell cycle distribution by flow cytometry. RESULTS: In the neoplastic cell lines indomethacin and ibuprofen caused a dose-dependent reduction of cell numbers and telomerase activity without altering cell viability and increased the percentage of cells in G0/G1 phase. In normal oral mucosal keratinocytes, only minor effects could be detected in response to NSAIDs and hydrocortisone. CONCLUSION: These results demonstrate that NSAIDs have activity against HNSCC cells in vitro and may have clinical applications in combination with other therapeutic regimens.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Carcinoma, Squamous Cell/pathology , Cell Cycle/drug effects , Head and Neck Neoplasms/pathology , Telomerase/antagonists & inhibitors , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/enzymology , Cell Division/drug effects , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/enzymology , Humans , Hydrocortisone/pharmacology , Ibuprofen/pharmacology , Indomethacin/pharmacology , Keratinocytes , Tumor Cells, Cultured
13.
Acta Otolaryngol ; 121(8): 957-62, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11813903

ABSTRACT

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.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Apoptosis/drug effects , Carcinoma, Squamous Cell/drug therapy , Head and Neck Neoplasms/drug therapy , Anti-Inflammatory Agents/pharmacology , Antibodies, Monoclonal/immunology , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Cyclin D1/drug effects , Cyclin D1/immunology , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/pathology , Humans , Keratinocytes/drug effects , Microscopy, Fluorescence/methods , Mouth Mucosa/pathology , Steroids , Tumor Cells, Cultured
14.
Int J Hyperthermia ; 16(5): 445-8, 2000.
Article in English | MEDLINE | ID: mdl-11001578

ABSTRACT

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 degrees C, 90 min) and in controls cultured under basal conditions (37 degrees C). Telomerase activity was strongly inhibited by hyperthermia and decreased in all cell lines tested after a recovery time of 2 h under basal conditions (37 degrees C) to an activity of approximately 85%, after 12 h approximately 60% and with lowest activity approximately 55% compared to activity of control cells. Telomerase 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.


Subject(s)
Hot Temperature , Osteosarcoma/enzymology , Telomerase/metabolism , Cell Division , Down-Regulation , Hot Temperature/therapeutic use , Humans , Hyperthermia, Induced , Osteosarcoma/metabolism , Osteosarcoma/pathology , Osteosarcoma/therapy , Time Factors , Tumor Cells, Cultured , Up-Regulation
16.
Radiologe ; 40(7): 596-600, 2000 Jul.
Article in German | MEDLINE | ID: mdl-10955289

ABSTRACT

Pathological conditions of the pharynx requiring diagnostic imaging (CT and/or MRI) are in increasing frequency malformations, inflammation, trauma, dysphagia and neoplasia. For neoplastic diseases CT/MRI are of major importance for pretherapeutic staging. Furthermore they should be used routinely in tumor follow up. Primary goal of diagnostic imaging of the pharynx is the analysis of submucosal structures that are not visible by clinical means. The close cooperation between otorhinolaryngology and radiology is necessary to define size, extent of tumor spread, infiltration and/or destruction of vital structures (vessels, nerves), leading to an individual therapeutic regimen.


Subject(s)
Pharyngeal Diseases/diagnosis , Pharynx/diagnostic imaging , Pharynx/pathology , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Tomography, X-Ray Computed
17.
Eur Arch Otorhinolaryngol ; 256(7): 351-5, 1999.
Article in English | MEDLINE | ID: mdl-10473829

ABSTRACT

The results of different forms of treatment of 37 patients with previously untreated glomus jugulare tumors were compared retrospectively. According to the Fisch classification system, 6 patients presented with class B tumors, 19 class C and 12 patients with class D. Twenty-eight patients underwent surgery and 9 patients had primary radiation therapy (to 50 Gy). In 20 of the surgical cases (71%), radical tumor removal could be achieved and required no further treatment over a follow-up period of 8.6 years (range 2-15 years). Incomplete tumor resection with postoperative radiation therapy resulted in progressive tumor growth in three cases. One patient in this group experienced subarachnoid bleeding that had to be managed by salvage surgery. After primary radiation therapy, glomus jugulare tumors were still evident on magnetic resonance imaging scans, but showed no signs of disease progression. As a result of our experience, we found that a one-stage radical tumor resection performed in collaboration by otologic surgeons and neurosurgeons was the best treatment for patients with large glomus jugulare tumors.


Subject(s)
Glomus Jugulare Tumor/surgery , Neoadjuvant Therapy , Adolescent , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Disease Progression , Female , Follow-Up Studies , Glomus Jugulare Tumor/pathology , Glomus Jugulare Tumor/radiotherapy , Humans , Male , Middle Aged , Neoplasm Staging , Patient Care Team , Radiotherapy, Adjuvant , Retrospective Studies
18.
Eur Arch Otorhinolaryngol ; 256(5): 266-70, 1999.
Article in English | MEDLINE | ID: mdl-10392304

ABSTRACT

Cytokine production by fibroblasts is not only important for immunological and inflammatory reactions in the epidermis and mucosa, but also for growth and differentiation of epithelial cells. To characterize the role of fibroblasts in the oropharyngeal mucosa, the expression of a panel of cytokines and cytokine receptors by fibroblasts isolated from normal human oropharyngeal mucosa was investigated by enzyme-linked immunosorbent assay (ELISA), reverse transcribed polymerase chain reaction (RT-PCR) and flow cytometry (FACS). Oropharyngeal fibroblasts produced the proinflammatory cytokines interleukin 1 alpha (IL-1 alpha), IL-6 and IL-8 without addition of phorbol-12-myristate-13-acetate (PMA) or biological response modifiers, suggesting an active involvement of these cells in host defence mechanisms. Keratinocyte growth factor (KGF), a growth factor for epithelial cells, and the angiogenetic fibroblast growth factors acidic and basic FGF (aFGF, bFGF) were also synthesized. Expression of receptors for IL-1, IL-4, IL-6, platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) was found. These results indicate that oral fibroblasts are capable of producing a number of cytokines without the need for additional stimuli and emphasize their active regulatory role in the maintenance of the oral mucosa.


Subject(s)
Fibroblasts/physiology , Inflammation/immunology , Interleukin-1/biosynthesis , Interleukin-6/biosynthesis , Interleukin-8/biosynthesis , Mitogens/immunology , Oropharynx/metabolism , Base Sequence , Culture Techniques , DNA Primers/immunology , DNA, Complementary/genetics , DNA, Complementary/immunology , Enzyme-Linked Immunosorbent Assay , Fibroblast Growth Factors/genetics , Fibroblast Growth Factors/immunology , Fluorescent Antibody Technique , Humans , Inflammation/genetics , Interleukin-1/genetics , Interleukin-1/immunology , Interleukin-6/genetics , Interleukin-6/immunology , Interleukin-8/genetics , Interleukin-8/immunology , Mitogens/genetics , Molecular Sequence Data , Mouth Mucosa/immunology , Mouth Mucosa/metabolism , Oropharynx/immunology , Reverse Transcriptase Polymerase Chain Reaction
19.
Alcohol Clin Exp Res ; 23(6): 1102-7, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10397297

ABSTRACT

INTRODUCTION: Epidemiologic studies have provided evidence that chronic ethanol consumption is an independent risk factor in upper aerodigestive tract cancer, but the underlying mechanisms are largely unknown. METHODS: To examine ethanol effects on mucosal keratinocytes in vitro, we used a squamous cell carcinoma of the head and neck (SCCHN) cell line as a model and, to exclude line specific effects, two other cell lines. The influence of ethanol on proliferation (using [3H]thymidine uptake/cell number), cell cycle distribution, cytokeratin pattern, and growth factor receptor expression (using FACS analyses) was investigated. RESULTS: Ethanol increased in a dose dependent manner (tested range 10(-3) M to 10(-10) M) the [3H]thymidine uptake and cell number, with unaltered viability (>95%) in all concentrations. In all tested cell lines, addition of 10(-3) M ethanol caused: (a) a significant increase of cells in the S-phase of the cell cycle; (b) a shift of cytokeratin pattern that suggested inhibition of differentiation; and (c) significant upregulation of EGF, IL-4, and PDGF receptors. CONCLUSIONS: Our results demonstrated an increased proliferation and reduced differentiation induced by ethanol in mucosa derived neoplastic cells, which may enhance further growth of neoplastic cells. These effects may also be involved in the carcinogenesis of upper aerodigestive tract malignancies.


Subject(s)
Cell Differentiation/drug effects , Cell Division/drug effects , Ethanol/pharmacology , Animals , Carcinoma, Squamous Cell , Cell Cycle/drug effects , Dose-Response Relationship, Drug , Head and Neck Neoplasms , Humans , Mice , Mucous Membrane/cytology , Receptors, Growth Factor/drug effects , Receptors, Growth Factor/metabolism , Tumor Cells, Cultured/cytology , Tumor Cells, Cultured/drug effects
20.
Article in English | MEDLINE | ID: mdl-10095201

ABSTRACT

The present study aimed to examine the cytokine expression pattern of human oral mucosa-derived keratinocytes at the protein and RNA level. The mRNA expression was measured by a RT-PCR method and the protein production was determined by an ELISA technique. In freshly isolated oral keratinocytes, IL-1alpha (interleukin 1alpha), IL-6, IL-8, transforming growth factor beta, tumor necrosis factor alpha and basic fibroblast growth factor were detectable at the protein and mRNA level, whereas platelet-derived growth factor, acidic fibroblast growth factor and transforming growth factor alpha were found only at the mRNA level. There were no detectable signals of IL-2 and IL-4. The cytokine production at the protein level was independent of prior stimulation with phorbol myristate acetate. Our results show that human oral keratinocytes - under nonpathological conditions - produce a cytokine pattern quite similar to that of epidermal keratinocytes, which may have implications for further functional studies.


Subject(s)
Cytokines/metabolism , Keratinocytes/metabolism , Mouth Mucosa/metabolism , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Humans , Mouth Mucosa/cytology , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction
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