RESUMEN
BACKGROUND: Glioblastoma (GBM) is the most common and most aggressive form of brain cancer. After surgery, radiotherapy is the mainstay of treatment for GBM patients. Unfortunately, the vast majority of GBM patients fail responding to radiotherapy because GBM cells remain highly resistant to radiation. Radiotherapy-induced DNA damage response may correlate with therapeutic resistance. METHODS: Ionizing radiation (IR) was used to induce DNA damage. Cell proliferation and migration were detected by wound-healing, MTT and apoptosis assays. Dual-luciferase assays and Western blot analysis were performed to evaluate NF-κB activation and validate microRNA targets. Real-time PCR was used to study mRNA and microRNA levels. RESULTS: IR-induced DNA damage activated NF-κB in GBM cells which promoted expression of IL-6, IL-8 and Bcl-xL, thereby contributing to cell survival and invasion. Knockdown SENP2 expression enhanced NF-κB essential modulator (NEMO) SUMOylation and NF-κB activity following IR exposure. miR-181b targets SENP2 and positively regulated NF-κB activity. CONCLUSION: NF-κB activation by DNA damage in GBM cells confers resistance to radiation-induced death.
Asunto(s)
Neoplasias Encefálicas/genética , Cisteína Endopeptidasas/metabolismo , Glioblastoma/genética , MicroARNs/biosíntesis , Apoptosis/efectos de la radiación , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/radioterapia , Línea Celular Tumoral , Movimiento Celular/efectos de la radiación , Proliferación Celular/efectos de la radiación , Supervivencia Celular/efectos de la radiación , Cisteína Endopeptidasas/genética , Daño del ADN/genética , Daño del ADN/efectos de la radiación , Regulación Neoplásica de la Expresión Génica , Glioblastoma/patología , Glioblastoma/radioterapia , Humanos , MicroARNs/metabolismo , FN-kappa B/genética , Radiación Ionizante , Transducción de Señal/genética , Transducción de Señal/efectos de la radiaciónRESUMEN
OBJECTIVE: To discuss the surgical skills and clinical value of complete transperitoneal laparoscopic nephroureterectomy. METHODS: We collected and analyzed the clinical data of 25 patients (14 renal pelvic carcinoma and 11 carcinoma of ulreter, right side 15 and left side 10) who underwent complete transperitoneal laparoscopic nephroureterectomy for the upper urinary tract urothelial carcinoma (UUT-UC) in Peking University First Hospital from May 2010 to April 2011. RESULTS: All the operations were successfully done by one surgeon with standard 4 or 5 trocars technique. The mean operative time was 150 min (120-180 min), the blood loss about 20-100 mL (mean 40 mL) and no severe complications observed. The postoperative hospital stay was 4-6 days with an average length of 5.5 days. The mean follow-up was 5.5 (1-11) months. One of 19 patients underwent trans urethral resection of bladder tumour (TURBT) for recurrent non-muscle invasive bladder tumor. CONCLUSION: Complete transperitoneal laparoscopic nephroureterectomy is a minimally invasive, safe and effective way to treat UUT-UC. The patients recover soon and have a shorter length of stay.
Asunto(s)
Neoplasias Renales/cirugía , Laparoscopía , Nefrectomía/métodos , Uréter/cirugía , Neoplasias Ureterales/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Transicionales/cirugía , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Previous studies have demonstrated that the sonic hedgehog (Shh) pathway plays a neuro-protective role. However, whether the Shh pathway is induced by subarachnoid hemorrhage (SAH) has not been investigated. We sought to investigate Shh activation in the cortex in the early stage of SAH, and assessed the effect of cyclopamine (a specific inhibitor of the Shh pathway) on Shh pathway regulation and evaluated the impact of cyclopamine on SAH. We found that the Shh pathway was up-regulated in the cortex after SAH, and that blocking the Shh pathway increased cell apoptosis. Early brain damages, including brain edema, blood-brain barrier impairment, and cortical apoptosis were significantly aggravated following with cyclopamine treatment compared with vehicle treatment. Our results suggest that the Shh pathway should be activated in the brain after SAH, and plays a beneficial role in SAH development, possibly by inhibiting cerebral oxidative stress through induction of antioxidant and detoxifying enzymes.
Asunto(s)
Lesiones Encefálicas/metabolismo , Corteza Cerebral/metabolismo , Proteínas Hedgehog/metabolismo , Hemorragia Subaracnoidea/metabolismo , Animales , Apoptosis/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Edema Encefálico/complicaciones , Edema Encefálico/metabolismo , Edema Encefálico/patología , Lesiones Encefálicas/complicaciones , Lesiones Encefálicas/patología , Corteza Cerebral/lesiones , Masculino , Ratas , Transducción de Señal/efectos de los fármacos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/patología , Regulación hacia Arriba/efectos de los fármacos , Alcaloides de Veratrum/farmacologíaRESUMEN
The aim of the present study was to determine the efficacy of microsurgery treatment for parasagittal meningioma in the central gyrus region. A microsurgical technique was used to treat 26 patients with large parasagittal meningioma in the central gyrus region. The Rolandic and draining veins and the peritumoral normal brain tissue were retained, and the associated sagittal sinus was appropriately protected. A Simpson grade I, II or III resection was performed in 8 (30.8%), 12 (46.2%) and 6 (23.1%) patients, respectively, with no post-operative mortalities. Following treatment, 9 patients exhibited hemiparalysis. No tumor recurrence was found in 21 patients during the follow-up examination. The treatment protocol described in the current study included sufficient pre-operative imaging evaluations, a skilled microsurgical technique, improved protection of the Rolandic vein and treatment of the sagittal sinus, and was found to significantly increase the total tumor removal rate and decrease post-operative recurrence.