RESUMO
To date, the major role of HPV16E6 in cancer has been considered to be its ability to inhibit the p53 tumor-suppressor protein, thereby thwarting p53-mediated cytotoxic responses to cellular stress signals. Here, we show that HPV16E6-dependent c-fos oncogenic protein expression contributes to AP-1 complex formation under oxidative stress in SiHa cells (HPV16-positive squamous cell carcinoma of the cervix). In addition, we examined the role of HPV16E6 in TGF-α-induced c-fos expression and found that the c-fos protein expression induced by TGF-α is HPV16E6 dependent. Thus, our results provide the first evidence that HPV16E6 contributes to AP-1 complex formation after both ligand-dependent and independent EGFR activation, suggesting a new therapeutic approach to the treatment of HPV-associated tumors.
Assuntos
Proteínas Oncogênicas Virais/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Repressoras/metabolismo , Fator de Transcrição AP-1/metabolismo , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Oncogênicas Virais/genética , Proteínas Proto-Oncogênicas c-fos/genética , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Proteínas Repressoras/genética , Fator de Transcrição AP-1/genética , Fator de Crescimento Transformador alfa/metabolismo , Neoplasias do Colo do Útero/metabolismo , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologiaRESUMO
BACKGROUND: In a pilot study, we showed that topical administration of a tetracycline could decrease oral bacteria levels for 6âhours in patients who underwent oral cancer surgery combined with tracheotomy and flap reconstruction. This multicenter, randomized control trial aimed to investigate the effectiveness of topical application of tetracycline ointment for prevention of surgical site infection (SSI) associated with major oral cancer surgery. METHODS: One hundred seventeen patients who underwent oral cancer resection combined with neck dissection, flap reconstruction, and tracheotomy were divided randomly into an intervention group (nâ=â56) and a control group (nâ=â61). The intervention consisted of topical administration of tetracycline ointment on the dorsum of the tongue every 6âhours for 48âhours postoperatively. Factors relating to the occurrence of SSI in both groups were subjected to logistic regression analysis. RESULTS: SSI occurred in 11 patients (19.6%) in the intervention group and 22 patients (36.1%) in the control group. Multivariate analysis showed that a longer operating time and not receiving topical tetracycline were independent risk factors for development of SSI. CONCLUSION: Administration of topical tetracycline for 48âhours postoperatively is an effective way of preventing SSI after oral cancer surgery.
Assuntos
Antibacterianos/uso terapêutico , Carcinoma de Células Escamosas/cirurgia , Neoplasias Bucais/cirurgia , Infecção da Ferida Cirúrgica/prevenção & controle , Tetraciclina/uso terapêutico , Administração Tópica , Idoso , Antibacterianos/administração & dosagem , Feminino , Humanos , Masculino , Projetos Piloto , Retalhos Cirúrgicos , Tetraciclina/administração & dosagem , Resultado do TratamentoRESUMO
For decades, platinum drugs have been the mainstay of cancer treatment. However, over time, drug resistance develops, leaving few treatment options. Here we show that platelet-derived growth factor α receptor (PDGF α receptor)-mediated signaling plays a key role in hepatocyte growth factor (HGF) receptor (c-Met) upregulation, which in turn is thought to play an important role in chemotherapy resistance. PDGF α receptor inhibition eliminates cisplatin-dependent Met expression in cervical cancer cell lines. PDGF α receptor inhibitors are widely used in clinical settings, suggesting that the clinical translation of our findings could reduce the suffering of people from drug resistance.
Assuntos
Antineoplásicos/farmacologia , Cisplatino/farmacologia , Proteínas Proto-Oncogênicas c-met/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Transdução de Sinais , Regulação para Cima/efeitos dos fármacos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/patologiaRESUMO
Little attention has been given to the connection between maxillary growth and the emergence of articulation disorders among cleft palate patients who previously successfully attained normal articulation after undergoing primary palatoplasty. Follow-up assessment of 22 surgically treated unilateral cleft lip and palate patients who attained normal articulation before school entry revealed that, during mixed dentition, half the patients exhibited palatalized articulation and half retained normal articulation. To determine the possible effect on articulation of growth changes in dental arch dimensions, a comparison was made of deciduous dentition and mixed dentition oral cavity measurements. Indications are that palatalized articulation occurs in patients with a smaller anterior palatal volume, the presence of linguoversion teeth, and poorer growth ability. Results reveal the importance of early management of dental arch dimensions, and the need for periodic assessment and management of articulation even for patients who attain normal articulation subsequent to primary palatoplasty.