RESUMO
AIM: To explore the efficacy of PCI-24781, a broad-spectrum, hydroxamic acid-derived histone deacetylase inhibitor, in the treatment of gastric cancer (GC). METHODS: With or without treatment of PCI-24781 and/or cis-diamminedichloroplatinum (CDDP), GC cell lines were subjected to functional analysis, including cell growth, apoptosis and clonogenic assays. Chromatin immunoprecipitation and luciferase reporter assays were used to determine the interacting molecules and the activity of the enzyme. An in vivo study was carried out in GC xenograft mice. Cell culture-based assays were represented as mean ± SD. ANOVA tests were used to assess differences across groups. All pairwise comparisons between tumor weights among treatment groups were made using the Tukey-Kramer method for multiple comparison adjustment to control experimental-wise typeâ Iâ error rates. Significance was set at P < 0.05. RESULTS: PCI-24781 significantly reduced the growth of the GC cells, enhanced cell apoptosis and suppressed clonogenicity, and these effects synergized with the effects of CDDP. PCI-24781 modulated the cell cycle and significantly reduced the expression of RAD51, which is related to homologous recombination. Depletion of RAD51 augmented the biological functions of PCI-24781, CDDP and the combination treatment, whereas overexpressing RAD51 had the opposite effects. Increased binding of the transcription suppressor E2F4 on the RAD51 promoter appeared to play a major role in these processes. Furthermore, significant suppression of tumor growth and weight in vivo was obtained following PCI-24781 treatment, which synergized with the anticancer effect of CDDP. CONCLUSION: These data suggest that RAD51 potentiates the synergistic effects of chemotherapy with PCI-24781 and CDDP on GC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Rad51 Recombinase/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Benzofuranos/administração & dosagem , Sítios de Ligação , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/administração & dosagem , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Fator de Transcrição E2F4/metabolismo , Feminino , Inibidores de Histona Desacetilases/administração & dosagem , Humanos , Ácidos Hidroxâmicos/administração & dosagem , Camundongos SCID , Regiões Promotoras Genéticas , Rad51 Recombinase/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Fatores de Tempo , Transfecção , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
<p><b>OBJECTIVE</b>To evaluate the efficacy, safety, and defecation after one-stage transanal endorectal pull-through(TOSEPT) for Hirschsprung disease.</p><p><b>METHODS</b>Clinical data of 56 patients with Hirschsprung disease undergoing TOSEPT in the Third Hospital of Guangzhou Medical College between 2005 and 2011 were retrospectively analyzed. According to age at operation, the patients were divided into newborn group(n=21, surgery performed within 1 month after birth) and non-newborn group(n=35). Recovery period was defined as the period required for normal defecation pattern after operation. Intraoperative and postoperative parameters were compared.</p><p><b>RESULTS</b>The mean operative time was(121.5±39.2) minutes. The mean length of bowel resection was(17.6±4.2) cm. The mean intraoperative blood loss was(34.6±5.2) ml. The mean postoperative hospital stay was(7.2±3.6) days. Postoperative complication occurred in 6 patients(4 had enteritis and 2 had recurrent constipation) in whom 1 were considered as failure of TOSEPT because of redo-surgery or persistent problems in defecation. The remaining 53 patients had normal defecation pattern after(9.2±5.8) weeks of postoperative recovery period. Neonatal cases had significantly shorter operative time and postoperative hospital stay, and longer postoperative recovery period than non-neonatal cases(P<0.05). There were no significant differences in intraoperative blood loss and postoperative complication rate between the two groups(P>0.05).</p><p><b>CONCLUSIONS</b>TOSEPT is effective and safe in the management of patients with Hirschsprung disease. However, a postoperative recovery period is required for a normal defecation pattern. Although neonatal cases have significantly shorter operative time and postoperative hospital stay than non-neonatal cases, but longer postoperative recovery period should be consider when evaluating the outcome of TOSEPT.</p>
Assuntos
Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Canal Anal , Cirurgia Geral , Defecação , Seguimentos , Doença de Hirschsprung , Cirurgia Geral , Período Pós-Operatório , Reto , Cirurgia Geral , Estudos Retrospectivos , Resultado do TratamentoRESUMO
This paper describes a type of blood pressure monitor we have developed using 8031 chip microprocessor based on oscillometric method and the designs of hardware and software. Comparing the measurement results of oscillometric method with that of direct invasive measurement method, we find that the monitor is very useful in clinical applications. Finally in the paper, some improvements that can be made in the monitor are proposed.
