Effect of 17-allylamino-17-demethoxygeldanamycin (17-AAG) on Akt protein expression is more effective in head and neck cancer cell lineages that retain PTEN protein expression.

OBJECTIVES: The aim of this study was to evaluate the expression of Akt, PTEN, Mdm2 and p53 proteins in three different head and neck squamous cell carcinoma (HNSCC) cell lines (HN6, HN19 and HN30), all of them treated with epidermal growth factor (EGF) and 17-allylamino-17-demethoxygeldanamycin (17-AAG), an inhibitor of Hsp90 protein. MATERIAL AND METHODS: Immunofluorescence and western blot were performed in order to analyze the location and quantification, respectively, of proteins under the action 17-AAG and EGF. RESULTS: Treatment with EGF resulted in increased levels of Akt, PTEN and p53 in all cell lineages. The expression of Mdm2 was constant in HN30 and HN6 lineages, while in HN19 showed slightly decreased expression. Under the action 17-AAG, in HN6 and HN19, the expression of PTEN and p53 proteins was suppressed, while Akt and Mdm2 expression was reduced. Finally, in the HN30 cell lineage were absolute absence of expression of Akt, Mdm2 and p53 and decreased expression of PTEN. CONCLUSION: These data allow us to speculate on the particular utility of 17-AAG for HNSCC treatment through the inhibition of Akt protein expression, especially in the cases that retain the expression of PTEN protein.

Citotoxicidade do Viscum album L. em células de carcinoma epidermoide da cavidade bucal / Cytotoxicity of mistletoe (Viscum album L. ) in oral squamous cell carcinoma

O carcinoma epidermoide de cabeça e pescoço é uma doença bastante complexa com diversos fatores etiológicos, além de mudanças distintas das estruturas e bases moleculares as quais provocam determinados eventos que culminam no surgimento desses tumores. Globalmente, também é classificada como uma das doenças mais comuns desta região. Principalmente nos países europeus os extratos de Viscum album L. (VA) (mistletoe) vêm sendo utilizado como terapia coadjuvante, com resultados bastante promissores em diversos tipos de tumores malignos. Estudos in vitro demonstraram que vários tipos de VA são capazes de provocar efeitos citotóxicos em células de carcinoma, ativando a cascata apoptótica ou levando as células à necrose. Este estudo teve como objetivo verificar a ação de três tipos de extratos de VA, não estudados anteriormente: Iscador Qu Spezial, Iscador P e Iscador M, em células de linhagem de carcinoma epidermoide de língua (SCC9 e SCC25). A concentração de 0.3 mg/mL (IC50) dos fármacos foi capaz de levar essas células à apoptose. Foi concluído que os extratos de VA possuem efeito citotóxico nas células de carcinoma epidermoide de língua (SCC9 e SCC25), entretanto as SCC9 possuem maior resistência à ação dos fármacos. Iscador Qu Spezial e Iscador M possuem maior potencial citotóxico em ambas as células, quando comparado ao Iscador P.(AU)

Head and neck squamous cell carcinoma is a complex disease with several etiologic factors and different molecular changes that may trigger certain events; it is also globally one of the most common malignancies in this topography. Extracts from Viscum album L. (VA) (mistletoe) have been used as adjuvant therapies with promising results in several types of cancer, mainly in European countries. In vitro studies have demonstrated that various types of VA may have cytotoxicity in carcinoma cells, activating the apoptotic cascade or leading cells to necrosis. This study aimed to verify the effect of three types of VA extracts (Iscador Qu Spezial, Iscador P and Iscador M) in cell lines of squamous cell carcinoma of the tongue (SCC9 and SCC25), not previously studied. A concentration of 0.3 mg/mL (IC50) of the drugs was capable to induce apoptosis. It was concluded that VA extracts have a cytotoxic effect on SCC9 and SCC25 cell lines, but while SCC9 cell line was more resistant to the action of the drugs. Iscador Qu Spezial and Iscador M have higher cytotoxic potential in both cell lines compared to Iscador P.(AU)

Radiation induced a supra-additive cytotoxic effect in head and neck carcinoma cell lines when combined with plant extracts from Brazilian Cerrado biome.

OBJECTIVES: Antineoplastic effects of molecules derived from plants have recently gained increasing attention as an additive to traditional therapies. The aim of this study was to evaluate the cytotoxic activity of plant extracts from the Brazilian Cerrado biome associated with radiotherapy in head and neck carcinoma cells (HNSCC). MATERIALS AND METHODS: Fifteen extracts derived from five Cerrado plants were tested in HNSCC cell lines (SCC-25, SCC-9, FaDu) and keratinocyte cells (HaCat). Cell cytotoxicity of extracts and association extract/radiation (2Gy/min) was assessed by MTT assay. Cisplatin (50 µg/mL) was used as a positive control. Extracts with the major cytotoxic activity were selected and their IC50 concentrations were defined. Apoptosis was assessed using flow cytometric analysis. RESULTS: Ten isolated extracts resulted in moderate cytotoxicity (>20 and ≤ 50 % of viable cells), while three extracts induced severe cytotoxic effects (≤ 20 % of viable cells). Plant extracts treatment improved radiotherapy cytotoxicity in all cell lines. Although plant extracts are not as potent as cisplatin plus radiation, in FaDu cells, seven extracts associated with irradiation showed cytotoxic activity similar or better than the association of cisplatin and radiation. Hexanic extract of Erythroxylum daphinites could induce apoptosis in oral cancer cells; however, necrosis was the prevalent kind of death in FaDu cells treated with hexanic extract of Erythroxylum suberosum. CONCLUSIONS: Pre-treatment of HNSCC cells with the extract derived from Cerrado plants followed by irradiation induced a supra-additive cytotoxic effect. CLINICAL RELEVANCE: This study highlights the potential biological relevance of the Cerrado biome when associated with traditional therapy for cancer.

Atypical presentation of oral basaloid squamous cell carcinoma.

AIM: The purpose of this report is to present the clinical and histological features of a basaloid squamous cell carcinoma (BSCC) occurring in the retromolar trigone of a 59-year-old man and to relate its immunohistochemical characteristics. BACKGROUND: BSCC is an aggressive distinct variant of squamous cell carcinoma (SCC) requiring recognition as a separate entity from SCC due to its peculiar behavior. CASE REPORT: A clinical examination revealed a 12x07x07 mm nodular mass with a rubbery consistency, defined borders, covered by reddish mucosa and an absence of bleeding upon palpation. Histologically, nests and cords of closely packed, moderately pleomorphic basaloid cells with nuclear palisading along the periphery of the neoplastic nests surrounded by a fibrous stroma were found. SUMMARY: Since this tumor can mimic other neoplasms such as adenoid cystic carcinoma, neuroendocrine carcinoma, and basal cell adenocarcinoma, histological features are essential to differentiate between them. Furthermore, immunohistochemical testing can provide valuable diagnostic information that can have a profound impact on treatment options and the prognosis. CLINICAL SIGNIFICANCE: BSCC needs to be differentiated from other neoplasms as early as possible because of its adverse prognosis. Clinicians are advised to conduct a mucosal evaluation during oral examinations and take a thorough medical history which could ultimately save the life of a patient.

Expressão imunoistoquímica da ciclina D1 e do p16 em carcinoma epidermóide de boca: correlação com sistema TNM e localização / Cyclin D1 and p16 immunohistochemical expression in oral squamous cell carcinoma: correlation with TNM classification and location

Objetivo: Avaliar a expressão imunoistoquímica da ciclina D1 e do p16 (proteínas envolvidas nas vias de proliferação celular e utilizadas para determinar o prognóstico de neoplasias malignas) em carcinoma epidermóide de boca.Correlacionar a imunomarcação com o sistema TNM (Tamanho do tumor, presença de linfonodo metastático e metástase à distância) e com sua localização anatômica. Métodos: Trinta e quatro (34) blocos de parafina contendo fragmentos de biópsia incisional de carcinomas epidermóides bucais primários foram obtidos no Hospital Araújo Jorge da Associação de Combate ao Câncer em Goiás. Os dados dos pacientes quanto à localização anatômica eo Sistema TNM foram coletados dos prontuários. A expressão das proteínas ciclina D1 e p16 foi verificada através da técnica imunoistoquímica utilizando a Streptoavidina-Biotina no Laboratório de Patologia Bucal da Faculdade de Odontologia da Universidade de São Paulo (FOUSP). Resultados e Conclusões: Os resultados não revelaram diferença estatisticamente significativa entre o número médio de núcleos positivos para a ciclina D1 e os dados clínicos dos pacientes. Porém, uma menor porcentagem de marcação nos carcinomas de lábio inferior e menor expressão nos tumores classificados clinicamente como T1 foi encontrada. Não houve diferença estatisticamente significativa entre o número médio de núcleos p16 positivos e os dados clínicos dos pacientes com carcinoma epidermóide de boca. Pode-se sugerir que houve um acúmulo nuclear de p16, mas este resultado não tem significância no prognóstico. Entretanto, os resultados da ciclina D1 não mostraram que ela é um marcador absoluto de prognóstico, mas sugerem que o aumento do nível de ciclina D1 contribui junto com outros oncogenes no processo de progressão tumoral.