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OBJECTIVE: This pilot study aimed to evaluate the efficacy and safety of domperidone for the treatment of Chinese patients with functional dyspepsia (FD) who were diagnosed according to the Rome IV criteria and to identify the FD subtypes that potentially responded better to domperidone. METHODS: This multicenter prospective study was conducted in China from August 2018 to July 2020, consisting of a 1-week screening phase and a 2-week double-blind treatment phase. Participants were randomized to receive domperidone 10 mg or matching placebo tablets thrice daily for 14 days. The primary end-point was the overall treatment effect (OTE) response rate after 2-week therapy. RESULTS: Altogether 160 patients were included, with 80 patients in each group. The OTE response rate after 2-week therapy was significantly higher for domperidone compared with placebo (60.7% vs 46.0%; relative risk [RR] 1.318, 95% confidence interval [CI] 0.972-1.787). Moreover, the OTE response rate after 2-week domperidone or placebo treatment was 60.3% versus 54.9% for postprandial distress syndrome (PDS) (RR 1.098, 95% CI 0.750-1.607) and 60.6% versus 35.2% for overlapping PDS-epigastric pain syndrome (EPS) (RR 1.722, 95% CI 0.995-2.980). Adverse events were reported by seven patients in the domperidone group and 12 patients in the placebo group. None of the adverse events in the domperidone group were serious. CONCLUSION: Domperidone showed a positive pattern regarding OTE response rates after 2-week therapy compared to placebo in patients with FD, as well as in subtypes of PDS and overlapping PDS-EPS. No new safety issue was observed.
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Dispepsia , Adulto , Humanos , Dispepsia/tratamiento farmacológico , Domperidona/efectos adversos , Proyectos Piloto , Estudios Prospectivos , Método Doble Ciego , Resultado del TratamientoRESUMEN
OBJECTIVES: Functional constipation is a gastrointestinal disorder prevalent around the world. Lubiprostone is the first locally acting type-2 chloride channel activator to be used for treating constipation. This study aimed to evaluate the efficacy and safety of lubiprostone in Chinese adults with functional constipation. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled study. Patients with functional constipation were randomized to receive either lubiprostone (24 mcg twice daily) or placebo for 4 weeks. The primary end-point was the frequency of spontaneous bowel movements (SBMs) during the first week of treatment. The secondary end-points included the median time of the first SBM, SBM frequency at weeks 2, 3 and 4, weekly response rate of SBMs, the stool consistency score and average number of complete spontaneous bowel movements (CSBMs) per week. RESULTS: In total, 259 patients were randomized, with 130 in the lubiprostone group and 129 in the placebo group. SBM frequency was higher in the lubiprostone group (4.88 ± 4.09/wk) than that in the placebo group (3.22 ± 2.01/wk) at week 1 (P < 0.0001). SBM frequency was also higher in the lubiprostone group at weeks 2, 3 and 4. The average number of CSBMs and the stool consistency score in the lubiprostone group were significantly higher than that in the placebo group at each week. No drug-related serious adverse events (AEs) occurred. The most commonly reported AE was nausea. CONCLUSION: Lubiprostone was superior to placebo in treating Chinese patients with functional constipation, together with good safety profile.
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Agonistas de los Canales de Cloruro , Estreñimiento , Adulto , China , Agonistas de los Canales de Cloruro/efectos adversos , Estreñimiento/tratamiento farmacológico , Defecación , Método Doble Ciego , Humanos , Lubiprostona , Resultado del TratamientoRESUMEN
BACKGROUND: Intramural esophageal bronchogenic cyst is very rare. Surgical removal of the cysts is advised even the patients are asymptomatic, since the cyst can lead to complications, and there is a risk of malignant transformation. Thoracotomy or thoracoscopy is the most commonly used approach for complete excision of the cysts. To our knowledge, this is the first report to excise intramural esophageal bronchogenic cyst completely by endoscopic submucosal tunnel dissection (ESTD). CASE PRESENTATION: A 40-year-old male was referred to our hospital due to the detection of a submucosal tumor at the distal esophagus. The tumor was found during gastroendoscopy in a general health check-up. The patient had no symptoms. A benign esophageal tumor was confirmed by endoscopic ultrasonography (EUS) and computed tomography (CT). On the basis of these results, ESTD was performed. During the procedure, a cystic mass was observed between the mucosa and the muscular layers of the esophagus, and a hybrid knife was used for dissection. Histopathological examination showed the cyst wall was lined by pseudostratified ciliated columnar epithelium, consistent with a bronchogenic cyst. The esophagography using meglumine diatrizoate showed no leakage on the seventh day after ESTD. The patient remained asymptomatic and had a regular diet during the follow-up period. DISCUSSION AND CONCLUSIONS: We successfully utilized ESTD for complete removal of esophageal bronchogenic cysts originating from the muscularis propria. The approach appeared safe, providing a minimally invasive treatment option for patients.
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Quiste Broncogénico/cirugía , Resección Endoscópica de la Mucosa/métodos , Quiste Esofágico/cirugía , Adulto , Quiste Broncogénico/diagnóstico por imagen , Quiste Esofágico/diagnóstico por imagen , Esofagoscopía , Humanos , Masculino , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
Kinetochoreassociated proteins are critical components of mitotic checkpoints, which are essential for faithful chromosomal segregation and spindle assembly during cell division. Recent advances have demonstrated that kinetochoreassociated proteins are upregulated and serve significant roles in the carcinogenesis of numerous types of cancer. However, the effects of kinetochoreassociated protein 1 (KNTC1) on human cancer, particularly on esophageal squamous cell carcinoma (ESCC), remain unclear. The present study revealed that KNTC1 was highly expressed in ESCC cell lines. Subsequently, lentivirusmediated short hairpin RNAs were used to knockdown KNTC1 expression in human ESCC cell lines. Cell growth and viability were measured using multiparametric highcontent screening and the MTT assay, respectively. Cell apoptosis was assessed by staining cells with Annexin Vallophycocyanin and was detected using FACScan flow cytometry. The results demonstrated that knockdown of KNTC1 effectively inhibited cell viability and increased apoptosis. In addition, a gene set enrichment analysis of online ESCC datasets indicated that KNTC1 overexpression was associated with increases in the mitotic spindle and hypoxia pathways, and decreases in the DNA repair and mismatch repair pathways. The findings of the present study suggested that KNTC1 may have an essential role in mediating cell viability and apoptosis in human ESCC cells and may serve as a novel therapeutic target for ESCC.
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Apoptosis , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Supervivencia Celular , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/patología , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Adulto , Apoptosis/genética , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Masculino , ARN Interferente Pequeño/metabolismo , Regulación hacia ArribaRESUMEN
The altered expression of miRNAs is involved in carcinogenesis of esophageal squamous cell carcinoma (ESCC), but whether miRNAs regulate COX-2 expression in ESCC is not clear. To this end, the expression levels of miR-26a and miR-144 in ESCC clinical tissues and cell lines were investigated by qRT-PCR. COX-2 and PEG2 were quantified by western blot and ELISA. Decrease in miR-26a and miR-144 expression in ESCC was found by a comparison between 30 pairs of ESCC tumor and adjacent normal tissues as well as in 11 ESCC cell lines (P < 0.001). Co-transfection of miR-26a and miR-144 in ESCC cell lines more significantly suppressed cell proliferation, migration, and invasion than did either miR-26a or miR-144 alone (all P < 0.001), as shown by assays of CCK8, migration and invasion and flow cytometry. The inhibitory effect of these two miRNAs in vivo was also verified in nude mice xenograft models. COX-2 was confirmed as a target of miR-26a and miR-144. In conclusion, miR-26a and miR-144 expression is downregulated in ESCC. Co-expression of miR-26a and miR-144 in ESCC cells resulted in inhibition of proliferation and metastasis in vitro and in vivo, suggesting that targeting COX-2 may be the mechanism of these two miRNAs.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/secundario , Proliferación Celular , Ciclooxigenasa 2/metabolismo , Neoplasias Esofágicas/patología , MicroARNs/genética , Animales , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Ciclo Celular , Movimiento Celular , Ciclooxigenasa 2/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones SCID , Metástasis de la Neoplasia , Pronóstico , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND & AIMS: Cyclooxygenase-2 (COX-2) is known to promote the carcinogenesis of esophageal squamous cell carcinoma (ESCC). There are no reports on whether microRNAs (miRNAs) regulate COX-2 expression in ESCC. This study investigated the effect of miR-101 on ESCC through modulating COX-2 expression in ESCC. METHODS: Real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR) was used to quantify miR-101 expression in ESCC clinical tissues and cell lines. The effects of miR-101 on ESCC progression were evaluated by cell counting kit-8 (CCK8), transwell migration and invasion assays, as well as by flow cytometry. The COX-2 and PEG2 levels were determined by western blot and enzyme-linked immunosorbent assays (ELISA). The luciferase reporter assay was used to verify COX-2 as a direct target of miR-101. The anti-tumor activity of miR-101 in vivo was investigated in a xenograft nude mouse model of ESCC. RESULTS: Downregulation of miR-101 was confirmed through comparison of 30 pairs of ESCC tumor and adjacent normal tissues (P < 0.001), as well as in 11 ESCC cell lines and a human immortalized esophageal cell line (P < 0.001). Transfection of miR-101 in ESCC cell lines significantly suppressed cell proliferation, migration, and invasion (all P < 0.001). The antitumor effect of miR-101 was verified in a xenograft model. Furthermore, COX-2 was shown to be a target of miR-101. CONCLUSIONS: Overexpression of miR-101 in ESCC inhibits proliferation and metastasis. Therefore, the miR-101/COX-2 pathway might be a therapeutic target in ESCC.
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Carcinoma de Células Escamosas/enzimología , Ciclooxigenasa 2/biosíntesis , Neoplasias Esofágicas/enzimología , Terapia Genética , MicroARNs/genética , Proteínas de Neoplasias/biosíntesis , ARN Neoplásico/genética , Animales , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Línea Celular Tumoral , Movimiento Celular , Ciclooxigenasa 2/genética , Regulación hacia Abajo , Inducción Enzimática/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Esófago/química , Regulación Neoplásica de la Expresión Génica/genética , Genes Reporteros , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/biosíntesis , Terapia Molecular Dirigida , Invasividad Neoplásica , Proteínas de Neoplasias/genética , ARN Neoplásico/biosíntesis , Reacción en Cadena en Tiempo Real de la Polimerasa , Transfección , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Detection of esophageal dysplasia/early esophageal squamous cell carcinoma (ESCC) is essential for improving 5-year survival. The aim of this prospective study was to evaluate whether Lugol chromoendoscopy improves the detection of esophageal dysplasia/early ESCC in patients with esophageal symptoms in a low-incidence region in China. Eligible patients were randomly assigned into two groups who received routine endoscopy or Lugol chromoendoscopy. During endoscopy, between one and five biopsies were taken from visible lesions for routine endoscopy, or unstained areas of >0.5 cm in diameter for Lugol chromoendoscopy. In total, 812 patients were enrolled, 395 for routine endoscopy and 417 for Lugol chromoendoscopy. The overall detection rate of esophageal dysplasia/early ESCC was 10.6% (86/812), the detection rates were 7.3% (29/395) and 13.7% (57/417) in routine and chromoendoscopy groups, respectively (χ2=8.58, P=0.003). The detection rates were 8.3% (48/580), 17.2% (17/99) and 16.5% (22/133), respectively, in patients with reflux, dysphagia and globus sensation symptoms. In the chromoendoscopy group, 213 patients had unstained lesions of >0.5 cm, the detection rates of dysplasia/early carcinoma were 5.3% (4/76) in those with lesions of 0.5-1.0 cm, and 37.2% (51/137) in those with lesions >1.0 cm (χ2=21.46, P<0.001). These results indicate that Lugol chromoendoscopy improves the detection rate of esophageal dysplasia/early carcinoma in patients with esophageal symptoms compared with routine endoscopy. We propose that Lugol chromoendoscopy must therefore be considered in addition to routine endoscopy in patients with esophageal symptoms.
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AIM: To study the relationship between the cyclooxygenase (COX)-2 gene and the proliferation and apoptosis of esophageal squamous carcinoma EC109 cells. METHODS: The techniques of RNA interference (RNAi) and cell transfection, as well as the levels of oncogenicity in nude mice, were used to study the role of COX-2 in the esophageal squamous carcinoma cell (ESCC) line EC109. Following RNAi and transfection, Western blotting analysis was used to determine the expression of the COX-2 protein. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) reduction assay was used to evaluate cell growth, and flow cytometry was used to detect cell apoptosis. RESULTS: Western blotting analysis demonstrated that COX-2 expression was significantly reduced in EC109 cells treated with COX-2-specific short interfering RNA (siRNA) but was increased in EC109 cells transfected with COX-2. Furthermore, COX-2 siRNA treatment inhibited cell proliferation (P < 0.01) and induced apoptosis in EC109 cells, as determined by an MTT assay and by flow cytometry, respectively. In contrast, transfected COX-2 led to increased cell proliferation (P < 0.05) and decreased apoptosis in EC109 cells. In addition, combination treatment of cells with COX-2 siRNA and aspirin had a synergistic effect (P < 0.01). For experiments measuring tumorigenicity, xenograft tumors of a greater volume and weight were found in the COX-2 group compared with other groups (P < 0.05). A large dose of aspirin inhibited tumor growth in nude mice effectively (P < 0.05), and the rate of tumor suppression was 51.8% in the high-dose aspirin group. CONCLUSION: COX-2 plays a very critical role in ESCC carcinogenesis, and COX-2 siRNA combined with aspirin has the potential to be an anticancer therapy for the treatment of ESCC.
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Carcinoma de Células Escamosas/enzimología , Ciclooxigenasa 2/metabolismo , Neoplasias Esofágicas/enzimología , Animales , Apoptosis/efectos de los fármacos , Aspirina/farmacología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/fisiopatología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Ciclooxigenasa 2/genética , Inhibidores de la Ciclooxigenasa/farmacología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/fisiopatología , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Interferencia de ARN , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , TransfecciónRESUMEN
Cyclooxygenase-2 (COX-2) has been shown to be upregulated in a variety of tumors so that COX-2 may be a potential target in the treatment of cancer. In order to further explore the mechanism, we used RNA interference to study effects of the inhibition of COX-2 on esophageal squamous cell carcinoma (ESCC) lines. Western blot analysis demonstrated that COX-2 expression was significantly reduced in ESCC cells treated with the COX-2-specific siRNA. Furthermore, the COX-2 siRNA treatment inhibited cell proliferation and induced apoptosis in ESCC cells. In addition, the combination treatment of COX-2 siRNA and acidum acetil salicylicum (aspirin) has a synergistic effect. Therefore, this combination has potential as an anticancer therapy for the treatment of ESCC.