RESUMEN
BACKGROUND: In this study, a combination of recombinant adenoviral p53 (rAd-p53) gene therapy and intra-arterial delivery of chemotherapeutic agents for treatment of oral squamous cell carcinoma was evaluated. METHODS: In total, 99 patients with stage III or IV oral carcinoma who had refused or were ineligible for surgery were enrolled in a randomized, placebo-controlled, double-blind, phase III clinical trial. They were randomly assigned to group I (n = 35; intra-arterial infusion of rAd-p53 plus chemotherapy), group II (n = 33; intra-arterial infusion of rAd-p53 plus placebo chemotherapy), or group III (n = 31; intra-arterial infusion of placebo rAd-p53 plus chemotherapy). RESULTS: The median length of follow-up was 36 months (range, 3 to 86 months). During follow-up, 16 patients in group I, 20 in group II, and 22 in group III died. Group I (48.5%) had a higher complete response rate than groups II (16.7%) and III (17.2%) (P = 0.006). The rate of non-responders in group I was significantly lower than that in groups II and III (P < 0.020). A log-rank test for survival rate indicated that group I had a significantly higher survival rate than group III (P = 0.019). The survival rate of patients with stage III but not stage IV oral cancer was significantly higher in group I than in group III (P = 0.015, P = 0.200, respectively). The survival rate of patients with stage IV did not differ significantly among the three groups. Or the 99 patients, 63 patients experienced adverse events of either transient flu-like symptoms or bone marrow suppression, while 13 patients had both these conditions together. No replication-deficient virus was detected in patient serum, urine, or sputum. rAd-p53 treatment increased Bax expression in the primary tumor of 80% of patients, as shown by immunohistochemical staining. CONCLUSIONS: Intra-arterial infusion of combined rAd-p53 and chemotherapy significantly increased the survival rate of patients with stage III but not stage IV oral cancer, compared with intra-arterial chemotherapy. Intra-arterial infusion of combined rAd-p53 and chemotherapy may represent a promising alternative treatment for oral squamous cell carcinoma. TRIAL REGISTRATION: ChiCTR-TRC-09000392 (Date of registration: 2009-05-18).
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Adenoviridae/genética , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Genes p53/genética , Terapia Genética/métodos , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/genética , Adulto , Anciano , Antineoplásicos/administración & dosificación , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Infusiones Intraarteriales , Masculino , Persona de Mediana Edad , Proyectos Piloto , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/genéticaRESUMEN
OBJECTIVE: To compare the clinical efficacy of the infiltration anesthesia with primacaine and the nerve blocking anesthesia with lidocaine for microport extraction of impacted lower third molar. METHODS; 104 chosen patients had both sides of impacted lower third molars extracted in this study. Patients were given local anesthesia with either primacaine or lidocaine randomly at each side, and then underwent microport extraction. Clinical factors including effective proportion (EP), effecting time point (ETP), visual analogue scale of pain (VASp), alteration of systolic pressures (ASP) and analgesia duration (AD) were evaluated statistically by means of paired t-test. RESULTS: The EP of experimental group was higher than the control group (P = 0.024). The ETP of soft tissue and alveoli-dental pulp was (1.04 +/- 0.21), (2.44 +/- 2.60) min in the experimental group, and much earlier than that of the control group (P = 0.002, P = 0.032). The VASp and ASP of experimental group were lower than the control group (P = 0.041, P = 0.018). AD was (103.6 +/- 35.5) min, and higher than the control group (P = 0.04). CONCLUSION: The infiltration anesthesia with primacaine has been proven to be a easier, reliable and quick-acting method. We suggest it an alternative method replacing the 2% lidocaine blocking during microport extraction of impacted lower third molar.
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Carticaína , Lidocaína , Adulto , Anciano , Anestesia Dental , Anestesia Local , Anestésicos , Anestésicos Locales , Pulpa Dental , Prueba de la Pulpa Dental , Método Doble Ciego , Femenino , Humanos , Masculino , Mandíbula , Nervio Mandibular , Diente Molar , Tercer Molar , Dimensión del Dolor , Estudios ProspectivosRESUMEN
AIM: To investigate the effect of DAPT (gamma-secretase inhibitor) on the growth of human tongue carcinoma cells and to determine the molecular mechanism to enable the potential application of DAPT to the treatment of tongue carcinoma. METHODOLOGY: Human tongue carcinoma Tca8113 cells were cultured with DAPT. Cell growth was determined using Indigotic Reduction method. The cell cycle and apoptosis were analyzed by flow cytometry. Real-time PCR and Immuno-Fluorescence (IF) were employed to determine the intracellular expression levels. RESULTS: DAPT inhibited the growth of human tongue carcinoma Tca8113 cells by inducing G0-G1 cell cycle arrest and apoptosis. The mRNA levels of Hairy/Enhancer of Split-1 (Hes-1), a target of Notch activation, were reduced by DAPT in a dose-dependent manner. Coincident with this observation, DAPT induced a dose-dependent promotion of constitutive Caspase-3 in Tca8113 cells. CONCLUSION: DAPT may have a therapeutic value for human tongue carcinoma. Moreover, the effects of DAPT in tumor inhibition may arise partly via the modulation of Notch-1 and Caspase-3.
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Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Carcinoma/patología , Dipéptidos/farmacología , Neoplasias de la Lengua/patología , Antineoplásicos/administración & dosificación , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/efectos de los fármacos , Caspasa 3/efectos de los fármacos , Línea Celular Tumoral , Membrana Celular/efectos de los fármacos , Núcleo Celular/efectos de los fármacos , Ciclina D1/efectos de los fármacos , Dipéptidos/administración & dosificación , Relación Dosis-Respuesta a Droga , Fase G1/efectos de los fármacos , Proteínas de Homeodominio/efectos de los fármacos , Humanos , Receptor Notch1/efectos de los fármacos , Proteínas Represoras/efectos de los fármacos , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Factor de Transcripción HES-1RESUMEN
OBJECTIVE: To investigate the differently expressed Homeobox genes between lingual squmaous cell carcinoma and normal mucosa. METHODS: Seven paired specimens including lingual squmaous cell carcinoma and its surrounding normal tissue were obtained from 7 patients. Customized Oligo microarray which contains numerous probes of 232 human Homeobox genes was used to analyse the results. All datas were scanned by Agilent scanner and differentiately expressed genes were sorted out. RESULTS: Homeobox gene NANOG was found up-regulated in 5 samples. PHTF2 was found down-regulated in 7 samples, and CRX, PITX1, OTEX was found down-regulated in 5 samples. CONCLUSION: As the key gene to cellular proliferation and differentiation, Homeobox genes is closely releverant to the oncogenesis of lingual squmaous cell carcinoma.
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Regulación Neoplásica de la Expresión Génica , Genes Homeobox , Diferenciación Celular , Humanos , Membrana MucosaRESUMEN
UNLABELLED: OBJECTIVE; To determine the clinical value of preoperative in vivo location of sentinel lymph node (SLN) by lymphoscintigraphy (LS) in oral carcinoma. METHODS: 10 patients with oral carcinoma were included in this study (7 male to 3 female). 99mTc-dextron was injected peritumorally 24 h before surgery. Lymphoscintigraphy images were obtained in anterior and lateral views. SLNs were detected and removed with the aid of dye during surgery. A standard radical neck dissection was then performed, and all lymph nodes were analyzed by HE staining. RESULTS: SLNs were successfully detected in 10 regions of 8 patients via lymphoscintigraphy. Consistent with the result of LS, 15 blue-stained SLNs were identified by means of dye method in 8 of 10 regions which the LS images indicated. CONCLUSION: This study suggests that preoperative in vivo location of SLN via lymphoscintigraphy should be helpful for the application of SLNB in oral carcinoma.
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Linfocintigrafia , Biopsia del Ganglio Linfático Centinela , Femenino , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Masculino , Neoplasias de la BocaRESUMEN
OBJECTIVE: To study the degeneration and regeneration of skeletal muscle after denervation. METHODS: Denervation was carried out in gastrocnemius muscles in 30 adult BALB/C mice by cutting the sciatic nerve. The gastrocnemius muscles were removed at 1, 2, 4, 8, 12, 16 weeks after denervation, respectively. Specimens were processed for histological study and immunohistochemical technique. RESULTS: Muscle fiber atrophy followed by degerneration and regeneration was observed in the early period of denervation. Fusion of the regenerated muscle cells with each other followed by degeneration of the cells and growth of fibro-connective tissue were observed in the later stage. The expression of myoglobin and actin decreased in 1-4 weeks after denervation. The postive expression of the proteins was observed in some 8 weeks' cells and in many degenerated 12-14 weeks' muscle cells. CONCLUSION: Degeneration and regeneration may coexisted in the denervated muscles. The regenerated muscle cells can't fully develop due to the deficit of nerve regulation and degenerate again. The regenerated muscle cells will melt each other and can't develop to mature muscle fiber in the later stage.