RESUMEN
Receptor-type protein tyrosine phosphatase κ (PTPRK) is considered to be a candidate tumor suppressor. PTPRK dephosphorylates CD133, which is a stem cell marker; phosphorylated CD133 accelerates xenograft tumor growth of colon cancer cells through the activation of AKT, but the functional significance of this has remained elusive. In this study, we have demonstrated that knockdown of PTPRK potentiates the pro-oncogenic CD133-AKT pathway in colon cancer cells. Intriguingly, depletion of PTPRK significantly reduced sensitivity to the anti-cancer drug oxaliplatin and was accompanied by up-regulation of phosphorylation of Bad, a downstream target of AKT. Together, our present observations strongly suggest that the CD133-PTPRK axis plays a pivotal role in the regulation of colon cancer progression as well as drug resistance.
Asunto(s)
Antígeno AC133/genética , Antineoplásicos/farmacología , Carcinogénesis/genética , Proliferación Celular/genética , Oxaliplatino/farmacología , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/genética , Antígeno AC133/metabolismo , Carcinogénesis/efectos de los fármacos , Línea Celular Tumoral , Progresión de la Enfermedad , Resistencia a Medicamentos , Células HEK293 , Células HT29 , Humanos , Fosforilación , Proteínas Tirosina Fosfatasas Clase 2 Similares a Receptores/metabolismo , Transducción de SeñalRESUMEN
BACKGROUND: Point-by-point catheter ablation is an established treatment for drug-refractory paroxysmal atrial fibrillation (PAF). However, it is time consuming, requires excellent technique to achieve complete pulmonary vein (PV) isolation, and is associated with severe complications. OBJECTIVES: The purpose of this study was to evaluate the safety and effectiveness of a HotBalloon ablation (HBA) compared with antiarrhythmic drug therapy (ADT) for the treatment of PAF. METHODS: A prospective multicenter randomized controlled study was conducted in Japan. Patients with symptomatic PAF refractory to antiarrhythmic drugs (Class I to IV) were randomized to HBA or ADT at a 2:1 ratio and assessed for effectiveness in a comparable 9-month follow-up period. RESULTS: A total of 100 patients in the HBA group and 43 patients in the ADT group received treatment at 17 sites. HBA procedure produced acute complete PV isolation in 98.0% (392 of 400) of the PVs and in 93.0% (93 of 100) of patients in the HBA group. The chronic success rates after the 9-month effective evaluation period were 59.0% in the HBA group (n = 100) and 4.7% in the ADT group (n = 43; p < 0.001). The incidence of major complications was 11.2% (15 of 134 patients). The incidences of PV stenosis (>70%) and transient phrenic nerve injury were 5.2% and 3.7%, respectively. The mean fluoroscopy time was 49.4 ± 26.6 min (n = 134), and the mean procedure duration was 113.9 ± 31.9 min (n = 133). CONCLUSIONS: This study demonstrates the superiority of HBA compared with ADT for treatment of patients with PAF, and a favorable safety profile.