Sensitizing TRAIL response via differential modulation of anti- and pro-apoptotic factors by AZD5582 combined with ER nanosomal TRAIL in neuroblastoma

xlomafota13 shared this article with you from Inoreader Sensitizing TRAIL response via differential modulation of anti- and pro-apoptotic factors by AZD5582 combined with ER nanosomal TRAIL in neuroblastoma Via histochem Acta Histochem. 2022 Jan 22;124(2):151856. doi: 10.1016/j.acthis.2022.151856. Online ahead of print. ABSTRACT Neuroblastoma is a metastatic brain tumor particularly common in children. The cure rate is below 50% for patients of high-risk condition. Novel therapeutic agents and approaches are needed to improve the cure rate. Tumor necrosis factor-related and apoptosis-inducing ligand (TRAIL) is a promising proapoptotic factor that rapidly induces apoptosis preferentially in t ransformed and cancerous cells. Unfortunately, the common TRAIL resistance in cancers has hampered the clinical application of the ligand. Previously we prepared a novel TRAIL-armed ER derived nanosomal agent (ERN-T) that overcomes TRAIL resistance in some cancer lines when combined with a synthetic antagonist of inhibitors of apoptosis proteins (IAPs), AZD5582. However, how AZD5582 sensitizes cancer cells to ERN-T remains not well understood. In this study we continued to test the therapeutic efficacy of the combinatory therapy of ERN-T and AZD5582 on neuroblastoma, aiming to reveal the molecular mechanism underlying the synergism between AZD5582 and ERN-T. The obtained data revealed that ERN-Ts overcame TRAIL resistance and showed significant cytotoxicity on the resistant neuroblastoma line SH-SH5Y when combined with AZD5582 whilst sparing normal cells. The combination of low doses of ERN-Ts and AZD5582 induced intensive apoptosis in SH-SY5Y but not in normal skin fibroblasts (NSF s). Importantly we discovered that TRAIL sensitization in SH-SY5Y was associated with the concomitant downregulation of antiapoptotic factors cFLIP, MCL-1 and IAPs and upregulation of proapoptotic protein BAX and the death receptor 5 (DR5) by the cotreatment of ERN-T and AZD5582. In vivo study demonstrated that the combination of ERN-T and AZD5582 constituted a highly effective and safe therapy for subcutaneous SH-SY5Y xenograft neuroblastoma in nude mice. In conclusion, we identified that the concomitant regulation of both antiapoptotic and proapoptotic factors and DR5 is an essential molecular mechanism for overcoming TRAIL resistance in SH-SY5Y and the combination of ERN-T and AZD5582 potentially constitutes a novel therapeutic strategy, which is highly effective and safe for neuroblastoma. PMID:35077998 | DOI:10.1016/j.acthis.2022.151856 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Primary Intracranial Neuroendocrine Tumor of the Skull Base Complicated with Tension Pneumocephalus after Radiotherapy

xlomafota13 shared this article with you from Inoreader Primary Intracranial Neuroendocrine Tumor of the Skull Base Complicated with Tension Pneumocephalus after Radiotherapy Via leak of cerebrospinal fluid NMC Case Rep J. 2021 Sep 16;8(1):609-615. doi: 10.2176/nmccrj.cr.2020-0367. eCollection 2021. ABSTRACT Neuroendocrine tumors (NETs) are neoplasms that originate from cells of the endocrine and nervous systems, and are commonly found in the gastrointestinal and respiratory tracts. Primary intracranial NETs are extremely rare and have been the focus of only a few studies thus far. Herein, we report the case of a primary intracranial NET of the skull base complicated with tension pneumocephalus after radiotherapy. An 84-year-old woman visited a local hospital for a head injury, and CT revealed a skull base tumor. MRI showed that the tumor was located mainly on the clivus and extended into the paranasal sinuses and nasal cavity. We biopsied the tumor via the nasal cavity, and the pathological diagnosis was NET, WHO grade 2. We subsequently administered focal intensity-modulated radiation therapy, but the patient developed tension pneumocephalus 1 year after radiotherapy. We therefore performed endoscopic transnasal cerebrospinal fluid leak closure with a nasoseptal flap. The postoperative course was successful, and the patient returned home but died of an unknown cause 2 years after discharge. The optimal postoperative management of primary intracranial NETs remains controversial. Tension pneumocephalus related to radiotherapy is a rare complication. Assessing skull bone erosion before radiotherapy and performing regular radiological follow-up examinations are essential to prevent this rare complication. PMID:35079524 | PMC:PMC8769468 | DOI:10.2176/nmccrj.cr.2020-0367 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Endoscopic Posterior Rotation Flap for Posterior Glottic Insufficiency

xlomafota13 shared this article with you from Inoreader Endoscopic Posterior Rotation Flap for Posterior Glottic Insufficiency Via The Laryngoscope View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.