ABSTRACT
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.
Subject(s)
Benzoquinones/pharmacology , Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/metabolism , Lactams, Macrocyclic/pharmacology , PTEN Phosphohydrolase/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Carcinoma, Squamous Cell/drug therapy , Cell Line, Tumor , Cell Lineage , Epidermal Growth Factor/pharmacology , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Head and Neck Neoplasms/drug therapy , Humans , Proto-Oncogene Proteins c-mdm2/metabolism , Squamous Cell Carcinoma of Head and Neck , Tumor Suppressor Protein p53/metabolismABSTRACT
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.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/radiotherapy , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Apoptosis/drug effects , Apoptosis/radiation effects , Brazil , Cell Line, Tumor , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Erythroxylaceae , Flow Cytometry , Humans , Keratinocytes/drug effects , Medicine, Traditional , Squamous Cell Carcinoma of Head and NeckABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell/diagnosis , Carcinoma, Transitional Cell/diagnosis , Mouth Neoplasms/diagnosis , Adenocarcinoma/diagnosis , Carcinoma, Adenoid Cystic/diagnosis , Carcinoma, Neuroendocrine/diagnosis , Carcinoma, Squamous Cell/pathology , Carcinoma, Transitional Cell/pathology , Cell Nucleus/ultrastructure , Diagnosis, Differential , Follow-Up Studies , Humans , Immunohistochemistry , Keratins/analysis , Ki-67 Antigen/analysis , Laminin/analysis , Male , Middle Aged , Mitosis , Mouth Neoplasms/pathology , Necrosis , Tumor Suppressor Protein p53/analysisSubject(s)
Mouth Neoplasms/pathology , Nose Neoplasms/pathology , Rhabdomyosarcoma, Alveolar/pathology , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Cranial Irradiation , Cyclophosphamide/administration & dosage , Cysts/diagnosis , Dactinomycin/administration & dosage , Diagnosis, Differential , Female , Humans , Mouth Mucosa/pathology , Mouth Neoplasms/diagnostic imaging , Mouth Neoplasms/drug therapy , Mouth Neoplasms/radiotherapy , Nasal Mucosa/pathology , Nose Neoplasms/diagnostic imaging , Nose Neoplasms/drug therapy , Nose Neoplasms/radiotherapy , Rhabdomyosarcoma, Alveolar/diagnostic imaging , Rhabdomyosarcoma, Alveolar/drug therapy , Rhabdomyosarcoma, Alveolar/radiotherapy , Ultrasonography , Vincristine/administration & dosageABSTRACT
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.