RESUMEN
Leukemia inhibitory factor receptor (LIFR) has been documented as a cancer promoter and to be present at high levels in various types of tumor tissues. In our search for molecules prognostic of colorectal cancer (CRC), we found high levels of LIFR in CRC tissue samples. Further analyses revealed that LIFR was indeed prognostic of CRC patient survival, and was associated with tumor size, lymphatic metastasis and stages. LIFR was found to promote tumor growth, metastasis and angiogenesis both in vitro and in vivo. High levels of LIFR in CRC facilitated proliferation and migration of endothelial cells, resulting in an increase in angiogenic activity. Moreover, interleukin 8 (IL-8) was found to play a role in the LIFR induced angiogenesis. IL-8 levels were correlated with LIFR levels in CRC tissues, whereas depletion of IL-8 led to a reduced angiogenic activity of LIFR in CRC cells. In addition, LIFR increased phosphorylation level of Erk, which regulates il-8 transcription. We conclude that LIFR is possibly a valuable prognostic marker for CRC. Our results also implicate a mechanism by which LIFR regulates tumor angiogenesis through Erk/IL-8 pathway, and that LIFR could be a potential therapeutic target for CRC.
Asunto(s)
Neoplasias Colorrectales/irrigación sanguínea , Células Endoteliales/patología , Interleucina-8/metabolismo , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/metabolismo , Neovascularización Patológica/patología , Anciano , Animales , Biomarcadores de Tumor/metabolismo , Línea Celular Tumoral , Proliferación Celular , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Regulación hacia Abajo , Femenino , Estudios de Seguimiento , Células Endoteliales de la Vena Umbilical Humana , Humanos , Interleucina-8/genética , Subunidad alfa del Receptor del Factor Inhibidor de Leucemia/genética , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Neovascularización Patológica/mortalidad , Pronóstico , ARN Interferente Pequeño/metabolismo , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Pure natural orifice transluminal endoscopic surgery (NOTES) for colorectal cancer is a complex procedure and rarely used in clinical practice because of the ethical concerns and technical challenges, including loss of triangulation, in-line orientation, and instrument collision. Transvaginal (v) NOTES, however, can overcome these technical challenges. We report a case of pure vNOTES right hemicolectomy for colon cancer, attached with surgical video. CASE SUMMARY: A 65-year-old woman with a 2-year history of intermittent diarrhea was diagnosed with ascending colon adenocarcinoma by colonoscopy and biopsy. Pure vNOTES right hemicolectomy was performed with complete mesocolic excision by well-experienced surgeons. The operative time was 200 min and the estimated blood loss was 30 mL. No intraoperative or postoperative complications occurred within 30 d after the surgery. The visual analog scale pain score on postoperative day 1 was 1 and dropped to 0 on postoperative days 2 and 3. The patient was discharged at postoperative day 6. The pathologic specimen had sufficient clear resection margins and 14 negative harvested lymph nodes. CONCLUSION: vNOTES right hemicolectomy, performed by well-experienced surgeons, overcomes the technical challenges of pure NOTES and may be feasible for colon cancer.