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BACKGROUND: Propofol is a common clinical intravenous anesthetic. In the last few years, studies have revealed that propofol not only has good anesthetic effect but also has certain anticancer effect. However, its role in stomach cancer (SC) and related mechanisms are still under investigation. OBJECTIVE: This study was designed to determine the effect of propofol on SC and its related mechanisms. METHODS: Purchased SC cells were treated with propofol at different concentrations (5, 10, and 20 µg/mL), miR-205 overexpression, and YAP1 inhibition. Then, the Cell Counting Kit-8 (CCK8), Transwell, and flow cytometry were carried out to determine the biological behavior changes of treated cells and the expression of miR-205 and YAP1 after treatment. RESULTS: Propofol (10 µg/mL and 20 µg/mL) inhibited the growth of SC cells and promoted their apoptosis, and overexpressing miR-205 or inhibiting YAP1 can exert the same effects. In addition, propofol (10µg/mL and 20µg/mL) up-regulated miR-205 in SC cells. The dual-luciferase reporter assay revealed that YAP1 could be targeted and regulated by miR-205, and the rescue assay revealed that inhibiting miR-205 or overexpressing YAP1 could weaken the effect of propofol on the biological behaviors of SC cells. CONCLUSION: Propofol can strongly suppress the proliferation and invasion of SC cells and induce their apoptosis via the miR-205/YAP1 axis.
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OBJECTIVE: This study retrospectively reviewed 46 cases of gastric gastrointestinal stromal tumors treated by endoluminal endoscopic full-thickness resection (EFR) microsurgery in our gastrointestinal endoscopy center. We aimed to evaluate the EFR for the treatment of gastric gastrointestinal stromal tumors originating from the muscularis propria. METHODS: A total of 46 patients with gastric gastrointestinal stromal tumors originated from the muscularis propria layer from January 2012 to June 2015 were treated with EFR. The patients were followed up with gastroscope and computed tomography (CT) for evaluation of therapeutic effect and safety. RESULTS: EFR was successfully accomplished to remove all tumors in 46 patients. The mean procedure time was 82.5±39.8min (56-188min). Except in 3 leiomyomas, pathological examination confirmed gastrointestinal stromal tumor (GIST) in 43 cases. None of the patients had occurred bleeding, peritonitis and other complications after EFR. Thereafter, all patients were followed up with gastro-scope after 1, 6,12 months. CONCLUSIONS: EFR is effective and safe for patients with gastric gastrointestinal stromal tumors originated from muscularis propria layer and has the advantage of less invasive treatment and higher tumor resection rate. It should be considered for further application.
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Resección Endoscópica de la Mucosa/métodos , Gastrectomía/métodos , Mucosa Gástrica/cirugía , Tumores del Estroma Gastrointestinal/cirugía , Leiomioma/cirugía , Neoplasias Gástricas/cirugía , Adulto , Anciano , Femenino , Mucosa Gástrica/patología , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Humanos , Leiomioma/patología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Gástricas/diagnóstico por imagen , Resultado del Tratamiento , Adulto JovenRESUMEN
SUMMARY OBJECTIVE: This study retrospectively reviewed 46 cases of gastric gastrointestinal stromal tumors treated by endoluminal endoscopic full-thickness resection (EFR) microsurgery in our gastrointestinal endoscopy center. We aimed to evaluate the EFR for the treatment of gastric gastrointestinal stromal tumors originating from the muscularis propria. METHODS: A total of 46 patients with gastric gastrointestinal stromal tumors originated from the muscularis propria layer from January 2012 to June 2015 were treated with EFR. The patients were followed up with gastroscope and computed tomography (CT) for evaluation of therapeutic effect and safety. RESULTS: EFR was successfully accomplished to remove all tumors in 46 patients. The mean procedure time was 82.5±39.8min (56-188min). Except in 3 leiomyomas, pathological examination confirmed gastrointestinal stromal tumor (GIST) in 43 cases. None of the patients had occurred bleeding, peritonitis and other complications after EFR. Thereafter, all patients were followed up with gastro-scope after 1, 6,12 months. CONCLUSIONS: EFR is effective and safe for patients with gastric gastrointestinal stromal tumors originated from muscularis propria layer and has the advantage of less invasive treatment and higher tumor resection rate. It should be considered for further application.
RESUMO OBJETIVO: Este estudo revisou retrospectivamente 46 casos de tumores gástricos estromáticos gastrointestinais tratados por microcirurgia endoluminal endoscópica de ressecção completa (EFR) em nosso centro de endoscopia gastrointestinal. Pretendemos avaliar a EFR para o tratamento de tumores gastrointestinais estromáticos originários da muscularis própria. MÉTODOS: Um total de 46 pacientes com tumores gástricos estromáticos gastrointestinais originários da camada muscular própria, de janeiro de 2012 a junho de 2015, foi tratado com EFR. Os pacientes foram acompanhados com gastroscópio e tomografia computadorizada (TC) para avaliação de efeitos terapêuticos e segurança. RESULTADOS: A EFR foi realizada com sucesso para remover todos os tumores em 46 pacientes. O tempo médio de procedimento foi de 82,5±39,8 min (56-188 min). Exceto em três leiomiomas, exame patológico confirmou tumor estromal gastrointestinal (Gist) em 43 casos. Em nenhum paciente ocorreu sangramento, peritonite e outras complicações após EFR. Posteriormente, todos os pacientes foram acompanhados com gastroscópio após um, seis e 12 meses. CONCLUSÕES: A EFR é eficaz e segura para pacientes com tumores gastrointestinais originários da camada muscular própria e tem a vantagem de ser um tratamento menos invasivo e com maior taxa de ressecção tumoral. Deve ser considerada para posterior aplicação.
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Humanos , Masculino , Femenino , Adulto , Anciano , Adulto Joven , Neoplasias Gástricas/cirugía , Tumores del Estroma Gastrointestinal/cirugía , Resección Endoscópica de la Mucosa/métodos , Gastrectomía/métodos , Mucosa Gástrica/cirugía , Leiomioma/cirugía , Neoplasias Gástricas/diagnóstico por imagen , Estudios Retrospectivos , Resultado del Tratamiento , Tumores del Estroma Gastrointestinal/diagnóstico por imagen , Mucosa Gástrica/patología , Leiomioma/patología , Persona de Mediana EdadRESUMEN
AIM: To assess the effectiveness of endoscopic full-thickness resection (EFR) and laparoscopic surgery in the treatment of gastric stromal tumors arising from the muscularis propria. METHODS: Out of 62 gastric stromal tumors arising from the muscularis propria, each > 1.5 cm in diameter, 32 were removed by EFR, and 30 were removed by laparoscopic surgery. The tumor expression of CD34, CD117, Dog-1, S-100, and SMA was assessed immunohistochemically. The operative time, complete resection rate, length of hospital stay, incidence of complications, and recurrence rate were compared between the two groups. Continuous data were compared using independent samples t-tests, and categorical data were compared using χ (2) tests. RESULTS: The 32 gastric stromal tumors treated by EFR and the 30 treated by laparoscopic surgery showed similar operative time [20-155 min (mean, 78.5 ± 30.1 min) vs 50-120 min (mean, 80.9 ± 46.7 min), P > 0.05], complete resection rate (100% vs 93.3%, P > 0.05), and length of hospital stay [4-10 d (mean, 5.9 ± 1.4 d) vs 4-19 d (mean, 8.9 ± 3.2 d), P >0.05]. None of the patients treated by EFR experienced complications, whereas two patients treated by laparoscopy required a conversion to laparotomy, and one patient had postoperative gastroparesis. No recurrences were observed in either group. Immunohistochemical staining showed that of the 62 gastric stromal tumors diagnosed by gastroscopy and endoscopic ultrasound, six were leiomyomas (SMA-positive), one was a schwannoglioma (S-100 positive), and the remaining 55 were stromal tumors. CONCLUSION: Some gastric stromal tumors arising from the muscularis propria can be completely removed by EFR. EFR could likely replace surgical or laparoscopic procedures for the removal of gastric stromal tumors.
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Gastrectomía/métodos , Tumores del Estroma Gastrointestinal/cirugía , Gastroscopía , Laparoscopía , Leiomioma/cirugía , Neurilemoma/cirugía , Neoplasias Gástricas/cirugía , Adulto , Anciano , Biomarcadores de Tumor/análisis , Distribución de Chi-Cuadrado , China , Femenino , Gastrectomía/efectos adversos , Tumores del Estroma Gastrointestinal/química , Tumores del Estroma Gastrointestinal/patología , Gastroscopía/efectos adversos , Humanos , Inmunohistoquímica , Laparoscopía/efectos adversos , Leiomioma/química , Leiomioma/patología , Tiempo de Internación , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Neurilemoma/química , Neurilemoma/patología , Tempo Operativo , Complicaciones Posoperatorias/terapia , Estudios Retrospectivos , Neoplasias Gástricas/química , Neoplasias Gástricas/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
Fluorouracil is the main chemotherapeutic drug used for gastrointestinal cancers, which suffers the important problem of treatment resistance. There is little information whether cannabinoid agonists can be used as an alternative drug for fluorouracil-resistant gastric cancer cells. In this study, we investigated the effects of a cannabinoid agonist, WIN-55,212-2, on 5-fluorouracil (5-FU)-resistant human gastric cancer cells, to examine whether the cannabinoid agonist may be an alternative therapy. Survival of the 5-FU-resistant gastric cancer cell line, SNU-620-5FU/1000, was not significantly reduced even by a high dose of 5-FU treatment. However, WIN-55,212-2 inhibited the proliferation of SNU-620-5FU/1000 and enhanced their apoptosis, as indicated by an increase of apoptotic cell proportion, activated caspase-3 and Poly (ADP-ribose) polymerase cleavage. Furthermore, WIN-55,212-2 reduced phospho-extracellular-signal-regulated kinases (ERK) 1/2, phospho-Akt (protein kinase B), B-cell lymphoma-2 (BCL2) and BCL2-associated X (BAX) protein expression in 5-FU-resistant gastric cancer cells. These results indicate that a cannabinoid agonist may, indeed, be an alternative chemotherapeutic agent for 5-FU-resistant gastric cancer.
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Benzoxazinas/farmacología , Agonistas de Receptores de Cannabinoides/farmacología , Morfolinas/farmacología , Naftalenos/farmacología , Receptores de Cannabinoides/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Antimetabolitos Antineoplásicos/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Resistencia a Antineoplásicos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fluorouracilo/farmacología , Humanos , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
For gastric cancers, the antineoplastic activity of cannabinoids has been investigated in only a few reports and knowledge regarding the mechanisms involved is limited. We have reported previously that treatment of gastric cancer cells with a cannabinoid agonist significantly decreased cell proliferation and induced apoptosis. Here, we evaluated the effects of cannabinoids on various cellular mediators involved in cell cycle arrest in gastric cancer cells. AGS and MKN-1 cell lines were used as human gastric cancer cells and WIN 55,212-2 as a cannabinoid agonist. Cell cycles were analyzed by flow cytometry and western blotting. Treatment with WIN 55,212-2 arrested the cell cycle in the G0/G1 phase. WIN 55,212-2 also upregulated phospho-ERK1/2, induced Kip1/p27 and Cip1/WAF1/p21 expression, decreased cyclin D1 and cyclin E expression, decreased Cdk 2, Cdk 4, and Cdk 6 expression levels, and decreased phospho-Rb and E2F-1 expression. ERK inhibitor decreased the proportion of G0/G1 phase which was induced by WIN 55,212-2. Inhibition of pAKT led to cell cycle arrest in gastric cancer cells. Cell cycle arrest preceded apoptotic response. Thus, this cannabinoid agonist can reduce gastric cancer cell proliferation via G1 phase cell cycle arrest, which is mediated via activation of the MAPK pathway and inhibition of pAKT.
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Benzoxazinas/farmacología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Morfolinas/farmacología , Naftalenos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Butadienos/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Línea Celular Tumoral , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Inhibidor p27 de las Quinasas Dependientes de la Ciclina/metabolismo , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/metabolismo , Relación Dosis-Respuesta a Droga , Factor de Transcripción E2F1/metabolismo , Inhibidores Enzimáticos/farmacología , Citometría de Flujo , Fase G1/efectos de los fármacos , Humanos , Proteína Quinasa 1 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/antagonistas & inhibidores , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Nitrilos/farmacología , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fase de Descanso del Ciclo Celular/efectos de los fármacos , Proteína de Retinoblastoma/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologíaRESUMEN
Although cannabinoids are associated with antineoplastic activity in a number of cancer cell types, the effect in gastric cancer cells has not been clarified. In the present study, we investigated the effects of a cannabinoid agonist on gastric cancer cell proliferation and invasion. The cannabinoid agonist WIN 55,212-2 inhibited the proliferation of human gastric cancer cells in a dose-dependent manner and that this effect was mediated partially by the CB(1) receptor. We also found that WIN 55,212-2 induced apoptosis and down-regulation of the phospho-AKT expression in human gastric cancer cells. Furthermore, WIN 55,212-2 treatment inhibited the invasion of gastric cancer cells, and down-regulated the expression of MMP-2 and VEGF-A through the cannabinoid receptors. Our results open the possibilities in using cannabinoids as a new gastric cancer therapy.
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Benzoxazinas/farmacología , Proliferación Celular/efectos de los fármacos , Morfolinas/farmacología , Naftalenos/farmacología , Invasividad Neoplásica/prevención & control , Receptor Cannabinoide CB1/agonistas , Neoplasias Gástricas/patología , Apoptosis/efectos de los fármacos , Secuencia de Bases , Línea Celular Tumoral , Cartilla de ADN , Regulación hacia Abajo/efectos de los fármacos , Citometría de Flujo , Humanos , Inmunohistoquímica , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND/AIMS: The lifestyle changes that have accompanied economic growth have influenced disease patterns in Korea. Changing patterns of gastrointestinal (GI) diseases over the past two decades were investigated in the present study. METHODS: Data from inpatients with specific GI diseases, as defined by the International Classification of Diseases code, were extracted from the database at a tertiary medical facility for 1990, 1996, and 2006. RESULTS: Admission rates for GI diseases increased between 1990 and 2006. The most prevalent disease in 1990 was gastric cancer, followed by appendicitis and colorectal cancer. However, by 2006, gastric cancer, colon cancer, and colon adenoma or polyps had become the most prevalent diseases. Although gastric cancer showed a decreasing trend, the rate of colon cancer doubled over two decades. Furthermore, rates of detection and endoscopic treatment of early gastric cancer and adenoma of the stomach and colon have increased noticeably. Newly emerging diseases include inflammatory bowel disease and gastroesophageal reflux. There was no change in the incidence of peptic ulcer, but ulcer-related complications and the numbers treated surgically decreased. CONCLUSIONS: The findings of this study indicate that the clinical trends of GI diseases in Korea have changed in a similar way to those in the West. Early detection of a GI neoplasm will continue to increase with the establishment of cancer-screening programs, resulting in a rising need for minimally invasive treatments.