Tolfenamic Acid Inhibits the Proliferation, Migration, and Invasion of Nasopharyngeal Carcinoma: Involvement of p38-Mediated Down-Regulation of Slug

PURPOSE: Tolfenamic acid (TA), a non-steroidal anti-inflammatory drug, is known to exhibit antitumor effects in various cancers apart from nasopharyngeal cancer (NPC). NPC exhibits high invasiveness, as well as metastatic potential, and patients continue to suffer from residual, recurrent, or metastatic disease even after chemoradiation therapy. Therefore, new treatment strategies are needed for NPC. In this study, we investigated the efficacy and molecular mechanisms of TA in NPC treatment. MATERIALS AND METHODS: TA-induced cell death was detected by cell viability assay in the NPC cell lines, HNE1 and HONE1. Wound healing assay, invasion assay, and Western blot analysis were used to evaluate the antitumor effects of TA in NPC cell lines. RESULTS: Treatment with TA suppressed the migration and invasion of HNE1 and HONE1 cells. Hepatocyte growth factor enhanced the proliferation, migration, and invasion abilities of NPC cells. This enhancement was successfully inhibited by TA treatment. Treatment with TA increased phosphorylation of p38, and the inhibition of p38 with SB203580 reversed the cytotoxic, anti-invasive, and anti-migratory effects of TA treatment in NPC cell lines. Moreover, inhibition of p38 also reversed the decrease in expression of Slug that was induced by TA treatment. CONCLUSION: In conclusion, the activation of p38 plays a role in mediating TA-induced cytotoxicity and inhibition of invasion and migration via down-regulation of Slug.

Aesthetic management of tooth discolouration: conservative treatment for a patient with undifferentiated nasopharyngeal carcinoma / Abordagem estética da descoloração dentária: tratamento conservador de um paciente com carcinoma nasofaríngeo indiferenciado

PURPOSE: Dental aesthetics has considerable impact in our beauty-conscious society. The darkening of the anterior teeth causes concern for adolescents due to the compromised physical appearance. This article presents a clinical case of tooth staining in an individual who had undergone radiotherapy/chemotherapy for an undifferentiated nasopharyngeal carcinoma. CASE DESCRIPTION: A 14-year-old boy presented to the dental clinic complaining of pain and staining of the maxillary and mandibular incisors, canines and premolars after having undergone radiotherapy/chemotherapy and stated his desire to remove the dark stains from the surface of the teeth due to his compromised oral aesthetics. Tooth whitening was performed with hydrogen peroxide, followed by micro-abrasion. At a two-year follow-up visit, clinical success was observed and the child was very satisfied. CONCLUSION: The adoption of such methods provided efficient alternatives for the re-establishment of a healthy smile, thereby returning pleasing facial aesthetics to the patient. The minimization of distress is nearly always the focus of clinical efforts at promoting psychological health in cancer survivors.

OBJETIVO: Atualmente, a estética dentária tem um impacto considerável na sociedade. O escurecimento dos dentes anteriores causa preocupação para os adolescentes, devido à aparência física comprometida. Este artigo apresenta um caso clínico de descoloração dentária em um indivíduo submetido a radioterapia/quimioterapia para tratamento de um carcinoma indiferenciado de nasofaringe. DESCRIÇÃO DO CASO: Um adolescente do gênero masculino, de 14 anos de idade, apresentou-se à clínica odontológica com queixa de dor e pigmentação dos incisivos superiores e inferiores, caninos e pré-molares após ter sido submetido a radioterapia/quimioterapia, declarando seu desejo de remover as manchas escuras na superfície do dentes comprometidos, devido à sua estética bucal. Foi realizado um clareamento dentário com peróxido de hidrogênio, seguido por micro-abrasão. Em um período de dois anos de seguimento, foi observado o sucesso clínico e a satisfação da criança. CONCLUSÃO: A adoção de tais métodos proporciona alternativas eficientes para o restabelecimento de um sorriso saudável, resgatando assim uma imagem facial agradável para o paciente. A minimização do sofrimento é geralmente o foco dos esforços clínicos visando a promoção da saúde psicológica em pacientes que sobreviveram ao câncer.

A Case of Wernicke's Encephalopathy Following Fluorouracil-based Chemotherapy

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.

Avaliação dos fatores clínicos e do tratamento em pacientes com carcinoma indiferenciado da nasofaringe / Assessment of clinical and therapeutic factors in patients with nasopharyngeal undifferentiated carcinoma

O carcinoma de nasofaringe é neoplasia rara, com incidência maior em países do Sudeste Asiático. OBJETIVO: Avaliar dados demográficos, clínicos, terapêuticos e prognósticos do carcinoma indiferenciado de nasofaringe em um serviço de referência. CASUÍSTICA E MÉTODO: Estudo retrospectivo de 46 pacientes, de janeiro de 1978 a agosto de 2000. Nenhum paciente foi previamente tratado e não apresentava tumor sincrônico e metástase à distância. RESULTADOS: A idade variou de 14 a 78 anos (média, 46), sendo 35 (76 por cento) pacientes masculinos. Todos eram de etnia caucasiana ou afro-brasileira. O tempo de história variou de 1 a 48 meses (média, 7), sendo 47 por cento tabagistas e 33 por cento etilistas. O sintoma mais relatado foi a presença de nódulo no pescoço (34 pacientes). Quanto ao estadiamento clínico, 22 foram estadiados como T1/T2 e 24 como T3/T4, enquanto 24 foram classificados como N2 e 16, N3. O tratamento instituído com finalidade curativa foi a radioterapia, associada à quimioterapia concomitante nos estádios III e IV. Dos 27 pacientes com seguimento após o tratamento inicial, 52 por cento apresentavam-se vivos e livres de doença há três anos. CONCLUSÃO: Os pacientes eram de estádio clínico avançado, com sobrevida livre de doença em três anos de 52 por cento.

The nasopharyngeal carcinoma (NPC) is a rare cancer with a high incidence in Southern Asia. AIM: to study the demographic, clinical, therapeutic, and prognostic factors of nasopharyngeal undifferentiated carcinoma in a reference service. MATERIALS AND METHODS: A retrospective study was made of 46 patients from January 1998 to August 2000. The patients had no previous treatment and did not present any evidence of synchronous tumors or distance metastases. RESULTS: The age ranged from 14 to 78 years (mean = 46 years); 35 (76 percent) patients were male. All patients were Caucasian or African-Brazilian. The onset of initial symptoms ranged from 1 to 48 months (mean = 7 months); 47 percent of the subjects smoked tobacco and 33 percent consumed alcoholic beverages. A lump in the neck was the most frequent symptom (34 patients). Twenty-two patients were clinically staged as T1/T2 and 24 patients as T3/T4; 24 patients were classified as N2, and 16 patients were staged as N3. Curative treatment consisted of radiotherapy and simultaneous chemotherapy in clinical stages III and IV. Of 27 patients that were monitored, 52 percent were alive with no evidence of disease after three years. CONCLUSION: All patients were in advanced clinical stages of the disease. The three-year disease-free survival rate was 52 percent.

Arsenic trioxide reduces the invasive and metastatic properties of nasopharyngeal carcinoma cells in vitro

Nasopharyngeal carcinoma (NPC) is notorious for the metastases, which are in close association with Epstein-Barr virus-encoded latent membrane protein 1 (LMP1). Arsenic trioxide (As2O3) has been shown to induce apoptosis and differentiation in NPC xenografts. Then, can it repress the cancer cells' metastasis potential? To elucidate this issue, the present study was performed. LMP1-negative cell line HNE1 and LMP1-positive cell line HNE1-LMP1 were used as in vitro model. Cells (1 x 10(5)/mL) were cultured with or without 3 æM As2O3 for 48 h. Then the survival cells were collected to investigate their potential of colony formation, attachment, invasion, and migration. Both confocal immunofluorescence staining and Western blot were used to detect the changes of LMP1 expression. The changes of MMP-9 were examined by RT-PCR assay and Western blot. The results were as follow: i) the colony formation inhibition rate (75.41 ± 3.9 percent in HNE1-LMP1 cells vs 37.89 ± 4.9 percent in HNE1 cells), the rate of attachment (HNE1-LMP1 vs HNE1: 56.40 ± 3.5 vs 65.87 ± 5.9 percent), the invasion inhibitory rate (HNE1-LMP1 vs HNE1: 56.50 ± 3.7 and 27.91 ± 2.1 percent), and the migration inhibitory rate (HNE1-LMP1 vs HNE1: 48.70 ± 3.9 vs 29.19 ± 6.27 percent) were all significantly different between the two cell lines (P < 0.01). ii) LMP1 was down-regulated in As2O3-treated HNE1-LMP1 cells. iii) The reduction of MMP-9 was found in As2O3-treated groups, more evident in HNE1-LMP1 cells. Thus, we conclude that As2O3 can reduce metastasis potential of NPC cells, involving inhibition of MMP-9 expression. LMP1 were also reduced in this process and seemed to enhance anti-metastasis activity of As2O3.

Differentiation of human nasopharyngeal carcinoma xenografts and repression of telomerase activity induced by arsenic trioxide.

BACKGROUND: Arsenic trioxide (As2O3) induced apoptosis and differentiation of acute promyelocytic leukaemia. A few in vivo experimental investigations of its efficacy in solid tumours have been done. This study was designed to explore the differentiation-inducing effect, and the possible mechanisms involved, of As2O3 on human nasopharyngeal carcinoma CSNE-1 xenografts. METHODS: Nasopharyngeal carcinoma cell CSNE-1 was established as a xenograft in nude mice. The tumour-bearing mice were treated with As2O3 at a dose of 5 mg/kg/day. To assess tumour differentiation, tumour growth was observed and histological changes were analysed under light and electron microscopy. Expression of latent membrane protein 1 (LMP1) and cytokeratin 4 (CK4) was determined by immunohistochemistry. A PCR-based telomeric repeat amplification protocol assay (TRAP-ELISA) was used to measure telomerase activity. RESULTS: The xenografts underwent differentiation. LMP 1 of the cells decreased significantly and there was a pronounced decline in telomerase activity. CONCLUSION: As2O3 can inhibit xenograft growth and induce morphological and functional differentiation of CSNE-1 cells. The As2O3-induced differentiation was associated with downregulation of telomerase activity.

Neoadjuvant chemotherapy and radiotherapy versus radiotherapy alone in patients with advanced nasopharyngeal carcinoma

A randomized study was carried out between January 1987 and December 1993 at the Kuwait Cancer Control Centre, to evaluate the efficacy of neoadjuvant chemotherapy and radiotherapy over radiotherapy alone inpatients with locally advanced nasopharyngeal carcinoma. Forty three patients were randomized to recive either neoadjuvant chemotherapy and radiotherapy [Combination arm] or radiotherapy alone. All the patients had stage IV disease. The tolerance to combination arm was inferior to that of radiation arm. There was no difference in the locoregional control rate between the two arms. Response rate following chemotherapy was 88%, which increased to 94% following radiotherapy. The overall response rate in the radiotherapy arm alone was 95%. At the median one of year of the follow up the failure rate in the radiotherapy arm was 26% and in the combination arm 24%. Three patients in the combination arm and two patients in the radiotherapy arm developed distant metastses

Photodynamic therapy for residual or recurrent cancer of the nasopharynx.

Adequate or effective treatments are not always available for most recurrent or residual nasopharyngeal cancers (NPC). Photodynamic therapy (PDT) using hematoporphyrin derivative (HpD) was evaluated for its effectiveness in treating patients, who conventionally failed, with curative or palliative intent. Thirteen patients were treated from March 1994 to November 1998. PDT was given to eradicate tumor cells, debulk tumor mass for other treatment options, and to resolve obstruction. Long-term tumor control could be achieved in 6 patients with localized lesions at T1-T2 stages. The mean disease free survival time was 25.8 months (range 5-61 months). For tumors beyond T2 stage (7 cases), PDT in combination with chemotherapy, laser surgery or radiotherapy induced complete response in 1 out of 5 patients (survival time = 40 months) and partial response in the rest (survival time = 16-37 months). In two patients who refused or were in tolerable to further treatment, PDT yielded useful palliative results (i.e. resolve nasal obstruction and epistaxis). On an overall basis, the average survival time for these patients with relatively advanced diseases was 24.7 months (range 9-40 months). Our study demonstrated that HpD-PDT could effectively control locally recurrent or residual NPC at T1-T2 stages and offered good palliation for more advances. Combined PDT and chemotherapy seemed to prolong survival time for a period longer than 2 years in T3-T4 tumors.

Phase II study: concurrent chemo-radiotherapy in advanced nasopharyngeal carcinoma.

This prospective clinical trial was conducted in previously untreated patients with stage IV nasopharyngeal carcinoma (TNM classification), who received concurrent chemo-radiotherapy regimen of cisplatin and radiation, followed by adjuvant chemotherapy consisting of 5FU and cisplatin. The aim was to improve both disease free survival and overall survival. From July 1991 to June 1993, 28 patients with stage IV (T1-4N2-3 M0) squamous cell carcinoma or undifferentiated cell carcinoma of the nasopharynx were treated at the Pramongkutklao Hospital with radical radiotherapy and concurrent chemotherapy using cisplatin 100 mg/m2 on day 1 and 22 of radiotherapy. Adjuvant chemotherapy consisted of cisplatin 100 mg/m2 day 1 and 5FU 800 mg/m2 continuous intravenous infusion 24 hours for day 1-4 and repeated every 4 weeks, for 4 courses. All twenty eight cases had documented stage IV without distant metastases. 11/28 and 16/28 had T4 and N3 disease respectively. The initial response to concurrent chemo-radiotherapy was 100 per cent (27 CR, and 1 PR). With a median follow-up period of 58 months, the 2-year and 4-year survival rates were 85 per cent and 78 per cent respectively. Concurrent chemo-radiotherapy and adjuvant chemotherapy was well tolerated and without significant acute or chronic toxic effect, only a few patients had grade 3 and 4 mucositis and hematologic toxicity. At median time to follow-up of 58 months, seven patients developed loco-regional recurrence and two had distant metastases at the time of analysis. The results of this prospective study demonstrated that concurrent chemo-radiotherapy could induce a durable complete remission in a high proportion of patients with poor-prognosis stage IV nasopharyngeal carcinoma, resulting in an improved overall 2 and 4-year survival when compared to historical control of radiation therapy alone.

Carcinoma nasofaríngeo: presentación de un caso, revisión de la literatura y de la casuística del Instituto Nacional de Pediatría de 1984-1994 / Nasopharynx carcinoma: a case report, review of literature and casuistry at the Instituto Nacional de Pediatría from 1984-1994

Se presenta el caso clínico de un paciente masculino de nueve años de edad con un año de evolución caracterizado por dolor intenso, hemifacila derecho, ataque al estado general, caracterizado por astenia, adinamia e hipodrexia, parálisis facial periférica izquierda y aumento de volumen cervical. La tomografía computada(TC), mostró tumoración que involucra la silla turca, seno cavernoso y fosa infratemporal derecha así como nasofaringe. El estudio histopatológico demostró ser carcinoma de nasofaringe. Se presenta el caso, se revisa la literatura y la casuística del Instituto Nacional de Pediatría de 1984 a 1994

Efficacy of chemoradiation therapy in patients with locally advanced nasopharyngeal carcinoma

External beam radiation therapy is the standard treatment for nasopharyngeal carcinoma. Recently there has been increasing interest of chemotherapy because of the high incidence of distant metastases and the sensitivity of these tumors to chemotherapy. Fourty two patients with locally advanced nasopharyngeal carcinomas were included in this study being either T3, T4, N2 or N3. Thirty one patients [71%] were under the age of 40 years. All patients were treated by 3 cycles of chemotherapy followed by external beam radiation. After three cycles of chemotherapy with cisplatinum and fluorouracil,the total response rate was 83% with a complete response rate of 38% [16/42] and partial response of 45% [19/42]. All patients recieved external beam radiation therapy to a dose of 7000 CGy at least and the complete response rate went up to 85.7% [36/42]. It was found that neither the tumor bulk nor the lymph nodes status in the neck correlated significantly to the response rate after chemotherapy. Patients having poorly differentiated squamous cell carcinoma or undifferentiated carciroma showed significantly better initial response to chemotherapy as compared to patients with moderaltely differentiated squamous cell carcinoma. No treatment related deaths were reported and all complication were reversible

Carcinoma of the nasopharynx in Iraq

50 Cases with histologically confirmed malignant tumors of the Nasopharynx were treated at the Institute of Radiology and Nuclear Medicine, Baghdad, over the period 1980-1984 inclusive/the majority of patients were in an advanced stage of the disease with cervical lymphadenopathy found in 78%. Radical Radiotherapy treatment was given in two phases with a total dose of 6500 CGY over 6-7 weeks. Combination chemotherapy in the from of Vincristine, Bleomycin and Methotrexate was given to 18 patients and five patients received cisplation combination in addition to radiotherapy. The five years survival rate was 64%. There were no statistical significant difference in the survival of those given chemotherapy in addition to radiotherapy. One patient developed radiation myelitis and died 3 years after therapy. A clear correlation between the stage of the disease and the prognosis was evident

Tratamiento radiante del cáncer de nasofaringe, experiencia del Instituto de Oncología y Radioterapia de Mar del Plata

Se analizaron los resultados terapéuticos de 28 pacientes con carcinoma de nasofaringe irradiados en el Instituto de Oncología y Radioterapia de Mar del Plata desde 1976 hasta 1984. El tratamiento consistió en radioterapia esclusiva en 23 pacientes y en 5 pacientes en radioterapia mas quimioterapia. La sobrevida global libre de enfermedad a los 3 años fue del 43,5%. El sitio en que con mayor frecuencia se observó fracaso terapéutico, fue el tumor primario. En efecto 13 pacientes (46%) fallaron en dicha área. Uno de los pacientes que recidivó en el tumor primario pudo ser rescatado con reirradiación del área nasofaringea. Se pone en evidencia en este trabajo la importancia de administrar dosis altas al tumor primario (> 7000 cGy) para obtener una mayor tasa de control local, y la necidad de lograr una combinación de agentes quimioterapéuticos más efectiva acrar una mayor proporción de pacientes con carcinoma de nasofaringe

Plasmocitoma localizado de rinofaringe / Located plasmocytoma of the rhinopharynx

Apresentam-se um caso de plasmocitoma extramedular recidivado de rinofaringe. Após uma cirurgia anterior em outra Instituiçäo da qual ficou assintomático por 6 anos, compareceu ao nosso Serviço com extensa recidiva, sendo considerado entäo, passível de tratamento quimioterápico, de onde tomou destino ignorado. Discutem-se a raridade do mieloma solitário, para seu diagnóstico, os critérios de Bichel e Kirketerp, ao lado da extrema raridade de sua localizaçäo nasofaríngea