RESUMO
OBJECTIVES: To explore the relationship between CADM1 expression and sensitivity to TPF-induced chemotherapy in laryngeal squamous cell carcinoma (LSCC) patients, then investigate its potential mechanisms. METHODS: Differential CADM1 expression was examined in chemotherapy-sensitive and chemotherapy-insensitive LSCC patient samples after TPF-induced chemotherapy using microarray analysis. Receiver operating characteristic (ROC) curve analysis and bioinformatics approaches were used to investigate the diagnostic value of CADM1. Small interfering RNAs (siRNAs) were used to knock down CADM1 expression in an LSCC cell line. Differential CADM1 expression was compared by qRT-PCR assays in 35 LSCC patients treated with chemotherapy, including 20 chemotherapy-sensitive and 15 chemotherapy-insensitive patients. RESULTS: Public database and primary patient data both suggest that CADM1 mRNA is expressed at lower levels in chemotherapy-insensitive LSCC samples, suggesting its potential usefulness as a biomarker. Knockdown of CADM1 with siRNAs led to decreased sensitivity of LSCC cells to TPF chemotherapy. CONCLUSIONS: Upregulation of CADM1 expression can alter the sensitivity of LSCC tumors to TPF induction chemotherapy. CADM1 is a possible molecular marker and therapeutic target for induction chemotherapy in LSCC patients.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Laríngeas , MicroRNAs , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/genética , Análise em Microsséries , RNA Interferente Pequeno/genética , Regulação Neoplásica da Expressão Gênica , Linhagem Celular Tumoral , Proliferação de Células , Molécula 1 de Adesão Celular/genética , Molécula 1 de Adesão Celular/metabolismoRESUMO
OBJECTIVE: To investigate the effects of telocinobufagin on viability and apoptosis of colorectal cancer (CRC) cells and explore the mechanism of telocinobufagin-induced apoptosis. METHODS: MTT assay was performed to detect the viability of CRC cells exposed to telocinobufagin. Nuclear staining with Hoechst 33342 and flow cytometry were used to analyze the cell death of CRC cells. Expressions of proteins related with cell apoptosis and oxidative stress were determined with Western blotting. RESULTS: Telocinobufagin decreased the viability of CRC cells in a time- and dose-dependent manner. The presence of karyopycnosis and apoptotic bodies together with the results of flow cytometry suggested that telocinobufagin induced cell apoptosis to cause cell death. Western blotting showed that telocinobufagin exposure of the cells resulted in upregulated p53 and Bax protein expressions and promoted cleavage of caspase 9 and PARP. Telocinobufagin induced phosphorylation of Bad and PARP cleavage, and suppressed phosphorylation of IKBα and TAK1 and expression of survivin in the cells. CONCLUSION: Telocinobufagin can decrease the viability of CRC cells by inducing cell apoptosis, which involves p53-mediated Bax activation and inhibition of the IAP pathway.
Assuntos
Apoptose , Bufanolídeos/farmacologia , Neoplasias Colorretais/patologia , Estresse Oxidativo , Caspase 9/metabolismo , Sobrevivência Celular , Humanos , MAP Quinase Quinase Quinases/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Células Tumorais Cultivadas , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/metabolismo , Proteína de Morte Celular Associada a bcl/metabolismoRESUMO
OBJECTIVE: To summarize the clinical effect of TPF regimen in the treatment of hypopharyngeal carcinoma and explore various clinical factors affecting treatment efficacy. METHOD: The clinical data of 20 cases with hypopharyngeal carcinoma, who received TPF treatment, were analyzed retrospectively. After two courses of chemotherapy, based on radiographic outcomes, next treatment plan was developed. To sum up the clinical information, including the clinical type, patterns of tumor growth, pathologic type, tumor stage, lymph node metastasis, age and so on. To analyze possible influencing factors affecting curative effect. RESULT: (1) After 20 cases with hypopharyngeal carcinoma received two courses of TPF treatment, the effect was evaluated. Objective response rate was 65%. (2) In patients with hypopharyngeal carcinoma, the efficacy of TPF therapy was significantly related to the clinical type, patterns of tumor growth and pathologic type; there was no statistical significance in tumor stage, lymph node metastasis and age. CONCLUSION: According to the clinical type, patterns of tumor growth and pathologic type of hypopharyngeal carcinoma, resistance to chemotherapy in hypopharyngeal carcinoma can be assessed, which provides important basis for designing individualized treatment plan.
