RESUMO
Background Gastric cancer (GC) is the second most common cause of cancer-related death worldwide. Novel anticancer drugs against gastric cancer are urgently needed. Methods Compound 10 was designed and synthesized via a molecular hybridization strategy based on the natural product formononetin. It was evaluated for their antiproliferative activity against three gastric cancer cell lines (SGC7901, MKN45 and MGC803). Results Derivative 10 displayed potently antiproliferative activity with an IC50 value of 1.07 µM against SGC7901 cells. Derivative 10 could inhibit the growth and migration against gastric cancer SGC7901 cells through the Wnt/ß-Catenin and AKT/mTOR pathways. From the in vivo expremints, it could effectively inhibited SGC7901 xenograft tumor growth in vivo without significant loss of the body weight. Conclusion Derivative 10 is an novel antitumor agent with potential for further clinical applications to treat gastric cancer. Graphical abstract.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Cumarínicos/uso terapêutico , Isoflavonas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cumarínicos/química , Cumarínicos/farmacologia , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Camundongos Nus , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Serina-Treonina Quinases TOR/metabolismo , Carga Tumoral/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacosRESUMO
Objective To observe the changes of esophageal pressure in patients with achalasia (AC) before and after peroral endoscopic myotomy (POEM), and to explore the value of high-resolution manometry (HRM) in evaluating the efficacy of POEM. Methods 38 cases were diagnosed as achalasia and treated with POEM from August 2015 to November 2016. Upper esophageal sphincter resting pressure (UESP), lower esophageal sphincter resting pressure (LESP), esophageal sphincter 4s integrated relaxation pressure (4sIRP) were detected by HRM before operation, at 1 week, 1 month after operation to evaluate the efficacy. Results A total of 38 patients with AC received POEM. At one week, one month after operation, the UESP were (45.34 ± 26.52) mmHg, (41.27 ± 20.09) mmHg, compared with that of before operation (49.58 ± 26.47) mmHg and the differences were not statistically significant. The differences in LESP, 4sIRP between before operation and at one week, one month after operation were statistically significant, P < 0.05. The differences in UESP, LESP and 4sIRP between 1 week and 1 month after operation were not statistically significant. Conclusion The pressure of lower esophageal sphincter was significantly reduced and the dysphagia was improved. HRM might play an important role in the assessment of AC received POEM.
RESUMO
Objective To observe the changes of esophageal pressure in patients with achalasia (AC) before and after peroral endoscopic myotomy (POEM), and to explore the value of high-resolution manometry (HRM) in evaluating the efficacy of POEM. Methods 38 cases were diagnosed as achalasia and treated with POEM from August 2015 to November 2016. Upper esophageal sphincter resting pressure (UESP), lower esophageal sphincter resting pressure (LESP), esophageal sphincter 4s integrated relaxation pressure (4sIRP) were detected by HRM before operation, at 1 week, 1 month after operation to evaluate the efficacy. Results A total of 38 patients with AC received POEM. At one week, one month after operation, the UESP were (45.34 ± 26.52) mmHg, (41.27 ± 20.09) mmHg, compared with that of before operation (49.58 ± 26.47) mmHg and the differences were not statistically significant. The differences in LESP, 4sIRP between before operation and at one week, one month after operation were statistically significant, P < 0.05. The differences in UESP, LESP and 4sIRP between 1 week and 1 month after operation were not statistically significant. Conclusion The pressure of lower esophageal sphincter was significantly reduced and the dysphagia was improved. HRM might play an important role in the assessment of AC received POEM.
