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2.
Infection ; 51(2): 489-495, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36178603

RESUMO

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.


Assuntos
Corynebacterium diphtheriae , Difteria , Refugiados , Humanos , Adulto Jovem , Adulto , Difteria/diagnóstico , Difteria/tratamento farmacológico , Áustria , Antitoxina Diftérica
3.
Cancer Invest ; 24(3): 242-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16809151

RESUMO

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.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Etoposídeo/uso terapêutico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Administração Oral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Resultado do Tratamento
4.
Br J Anaesth ; 96(5): 650-9, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16574723

RESUMO

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.


Assuntos
Ventilação em Jatos de Alta Frequência/métodos , Laringoestenose/cirurgia , Estenose Traqueal/cirurgia , Adulto , Idoso , Dióxido de Carbono/sangue , Feminino , Humanos , Laringoscópios , Laringoscopia , Terapia a Laser , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Pressão Parcial , Estudos Prospectivos
5.
Acta Neurochir (Wien) ; 144(12): 1255-64; discussion 1264, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12478336

RESUMO

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.


Assuntos
Avaliação de Resultados em Cuidados de Saúde , Paraganglioma/radioterapia , Paraganglioma/cirurgia , Radiocirurgia , Neoplasias Cranianas/radioterapia , Neoplasias Cranianas/cirurgia , Osso Temporal/efeitos da radiação , Osso Temporal/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Paraganglioma/patologia , Radioterapia Adjuvante , Estudos Retrospectivos , Neoplasias Cranianas/patologia , Osso Temporal/patologia , Fatores de Tempo
6.
Oncology ; 63(2): 145-50, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12239449

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Intervalo Livre de Doença , Docetaxel , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Cuidados Paliativos , Recidiva , Taxa de Sobrevida , Fatores de Tempo
7.
Laryngorhinootologie ; 81(8): 568-72, 2002 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-12189573

RESUMO

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.


Assuntos
Carcinoma Adenoescamoso , Neoplasias Palatinas , Idoso , Biópsia , Antígeno Carcinoembrionário/análise , Carcinoma Adenoescamoso/diagnóstico , Carcinoma Adenoescamoso/diagnóstico por imagem , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Diagnóstico Diferencial , Seguimentos , Humanos , Neoplasias Pulmonares/secundário , Metástase Linfática , Imageamento por Ressonância Magnética , Masculino , Neoplasias Palatinas/diagnóstico , Neoplasias Palatinas/diagnóstico por imagem , Neoplasias Palatinas/patologia , Neoplasias Palatinas/cirurgia , Palato Mole/patologia , Prognóstico , Retalhos Cirúrgicos , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Alcohol Clin Exp Res ; 25(4): 496-501, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11329487

RESUMO

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.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Depressores do Sistema Nervoso Central/farmacologia , Etanol/farmacologia , Neoplasias de Cabeça e Pescoço/metabolismo , Proteína do Retinoblastoma/efeitos dos fármacos , Proteínas rho de Ligação ao GTP/efeitos dos fármacos , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Fosforilação , RNA Mensageiro/efeitos dos fármacos , RNA Mensageiro/metabolismo , Proteína do Retinoblastoma/metabolismo , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Proteínas rho de Ligação ao GTP/metabolismo
9.
Anticancer Drugs ; 12(3): 205-8, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11290867

RESUMO

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.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , DNA Topoisomerases Tipo II , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Adulto , Idoso , Anemia/induzido quimicamente , Antígenos de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Proteínas de Ligação a DNA , Diarreia/induzido quimicamente , Feminino , Seguimentos , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Isoenzimas/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Mitoxantrona/efeitos adversos , Náusea/induzido quimicamente , Metástase Neoplásica , Recidiva Local de Neoplasia , Neutropenia/induzido quimicamente , Estomatite/induzido quimicamente , Inibidores da Topoisomerase II , Resultado do Tratamento , Vômito/induzido quimicamente
10.
Acta Otolaryngol ; 121(1): 103-9, 2001 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-11270487

RESUMO

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.


Assuntos
Calcitriol/farmacologia , Carcinoma de Células Escamosas/genética , Proteínas de Ciclo Celular , Ciclo Celular/efeitos dos fármacos , Ciclinas/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Supressoras de Tumor , Linhagem Celular , Inibidor de Quinase Dependente de Ciclina p21 , Inibidor de Quinase Dependente de Ciclina p27 , Ciclinas/genética , Citometria de Fluxo , Humanos , Immunoblotting , Proteínas Associadas aos Microtúbulos/genética , Reação em Cadeia da Polimerase , RNA/análise , Proteína do Retinoblastoma/análise , Células Tumorais Cultivadas
11.
J Oral Pathol Med ; 30(2): 91-7, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11168853

RESUMO

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.


Assuntos
Linfócitos B/patologia , Jejuno/transplante , Neoplasias Bucais/cirurgia , Neoplasias Orofaríngeas/cirurgia , Linfócitos T/patologia , Idoso , Anticorpos Monoclonais , Antígenos de Superfície/análise , Subpopulações de Linfócitos B/patologia , Biópsia , Endotélio Vascular/patologia , Feminino , Seguimentos , Granulócitos/patologia , Antígenos HLA-DR/análise , Humanos , Molécula 1 de Adesão Intercelular/análise , Cuidados Intraoperatórios , Jejuno/patologia , Células Matadoras Naturais/patologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Subpopulações de Linfócitos T/patologia , Transplante Autólogo , Molécula 1 de Adesão de Célula Vascular/análise
12.
Acta Otolaryngol ; 121(8): 957-62, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11813903

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anticorpos Monoclonais/imunologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Ciclina D1/efeitos dos fármacos , Ciclina D1/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Queratinócitos/efeitos dos fármacos , Microscopia de Fluorescência/métodos , Mucosa Bucal/patologia , Esteroides , Células Tumorais Cultivadas
13.
Head Neck ; 23(12): 1049-55, 2001 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11774390

RESUMO

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.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Carcinoma de Células Escamosas/patologia , Ciclo Celular/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/patologia , Telomerase/antagonistas & inibidores , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/enzimologia , Divisão Celular/efeitos dos fármacos , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/enzimologia , Humanos , Hidrocortisona/farmacologia , Ibuprofeno/farmacologia , Indometacina/farmacologia , Queratinócitos , Células Tumorais Cultivadas
14.
Int J Hyperthermia ; 16(5): 445-8, 2000.
Artigo em Inglês | MEDLINE | ID: mdl-11001578

RESUMO

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.


Assuntos
Temperatura Alta , Osteossarcoma/enzimologia , Telomerase/metabolismo , Divisão Celular , Regulação para Baixo , Temperatura Alta/uso terapêutico , Humanos , Hipertermia Induzida , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Osteossarcoma/terapia , Fatores de Tempo , Células Tumorais Cultivadas , Regulação para Cima
16.
Radiologe ; 40(7): 596-600, 2000 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-10955289

RESUMO

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.


Assuntos
Doenças Faríngeas/diagnóstico , Faringe/diagnóstico por imagem , Faringe/patologia , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X
17.
Eur Arch Otorhinolaryngol ; 256(7): 351-5, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10473829

RESUMO

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.


Assuntos
Tumor do Glomo Jugular/cirurgia , Terapia Neoadjuvante , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Progressão da Doença , Feminino , Seguimentos , Tumor do Glomo Jugular/patologia , Tumor do Glomo Jugular/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Equipe de Assistência ao Paciente , Radioterapia Adjuvante , Estudos Retrospectivos
18.
Eur Arch Otorhinolaryngol ; 256(5): 266-70, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10392304

RESUMO

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.


Assuntos
Fibroblastos/fisiologia , Inflamação/imunologia , Interleucina-1/biossíntese , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Mitógenos/imunologia , Orofaringe/metabolismo , Sequência de Bases , Técnicas de Cultura , Primers do DNA/imunologia , DNA Complementar/genética , DNA Complementar/imunologia , Ensaio de Imunoadsorção Enzimática , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/imunologia , Imunofluorescência , Humanos , Inflamação/genética , Interleucina-1/genética , Interleucina-1/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Mitógenos/genética , Dados de Sequência Molecular , Mucosa Bucal/imunologia , Mucosa Bucal/metabolismo , Orofaringe/imunologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa
19.
Alcohol Clin Exp Res ; 23(6): 1102-7, 1999 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10397297

RESUMO

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.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Etanol/farmacologia , Animais , Carcinoma de Células Escamosas , Ciclo Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neoplasias de Cabeça e Pescoço , Humanos , Camundongos , Mucosa/citologia , Receptores de Fatores de Crescimento/efeitos dos fármacos , Receptores de Fatores de Crescimento/metabolismo , Células Tumorais Cultivadas/citologia , Células Tumorais Cultivadas/efeitos dos fármacos
20.
Artigo em Inglês | MEDLINE | ID: mdl-10095201

RESUMO

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.


Assuntos
Citocinas/metabolismo , Queratinócitos/metabolismo , Mucosa Bucal/metabolismo , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Humanos , Mucosa Bucal/citologia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais
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