RESUMEN
Colorectal cancer (CRC) is a leading cause of cancer mortality worldwide. Although considerable advances in CRC treatment have been achieved, effective treatment improvement has hit a bottleneck. This study demonstrated that TYRO3 expression was aberrantly increased in CRC tissues with prognosis association. The prediction model of prognosis for CRC patients was constructed based on TYRO3 expression. The model suggested that the TYRO3 level is crucial to the final prediction results. We observed that knockdown TYRO3 expression could inhibit the proliferation and migration ability and reverse the drug resistance by constructing drug-resistant CRC cell lines. In vivo experiments also confirmed this conclusion. Thus, targeting TYRO3 combined with 5-Fu treatment could provide a better therapeutic effect. Additionally, TYRO3 could inhibit the EMT process by down-regulating ENO1, which may be achieved by interfering with energy metabolism in cancer cells. Therefore, the current study provides a theoretical basis for TYRO3 in drug-resistance of CRC cells and highlights a new strategy for CRC-targeted therapy.
Asunto(s)
Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Transición Epitelial-Mesenquimal/genética , Línea Celular Tumoral , Transformación Celular Neoplásica , Carcinogénesis/genética , Resistencia a Antineoplásicos/genética , Movimiento Celular/genética , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Tirosina Quinasas Receptoras/metabolismoRESUMEN
OBJECTIVE: To investigated the potential and safety of the monoclonal antibody to TNFalpha infliximab (IFX) in the treatment of active Crohn's disease (CD). METHODS: Patients who were confirmed diagnosis of CD and were unresponsive to the conventional treatments, or recurred after surgeries, or discontinued treatment due to drug intolerance, were treated with IFX intravenously in a dose of 5 mg/kg at week 0, 2, 6 (IFX infusion continued at an interval of every 8 weeks if respond to initial dosing). Clinical assessments, including disease activity, blood biological markers and colonoscopic findings, were performed at baseline (week 0) and each week (4 weeks or later for colonoscopy) after IFX infusion were conducted until the week before 4(th) infusion from initiated. RESULTS: Ten patients (8 male, 2 female) with mean age of 31.4 years (ranged from 15 to 65 years old) were included in the analysis. The mean subjective score from baseline to week 14 was decreased from 2.2 +/- 0.6 to 1.2 +/- 0.4 (P < 0.05). The mean Harvey-Bradshaw index was 6.6 +/- 1.6 at baseline and 2.1 +/- 1.0 at week 14. The levels of ESR, CRP, serum total protein (TP) and albumin (Alb) were significantly improved during the 14-week period. Colonoscopy showed a remarkable improvement of Crohn's Disease Endoscopic Index of Severity (CDEIS). No infusion-related reaction was observed in all patients during the treatment. Mild or transient skin itching and headache were respectively reported in two patients. Transient elevation of serum ALT and AST after 3(rd) infusion in one patient, and severe anemia including leucopenia and thrombocytopenia at week 35 after 1(st) infusion in one male patient were observed. CONCLUSIONS: Treatment with three infusions of IFX in a dose of 5 mg/kg was effective for induction of remission for active and complex CD patients who failed to respond to conventional treatment. Long-term safety of the therapy effect was warranted in further investigations.