Neuroblastoma (NB) is the most common extracranial solid tumor often diagnosed in childhood. Despite intense efforts to develop a successful treatment, current available therapies are still challenged by high rates of resistance, recurrence and progression, most notably in advanced cases and highly malignant tumors. Emerging evidence proposes that this might be due to a subpopulation of cancer stem cells (CSCs) or tumor-initiating cells (TICs) found in the bulk of the tumor. Therefore, the development of more targeted therapy is highly dependent on the identification of the molecular signatures and genetic aberrations characteristic to this subpopulation of cells. This review aims at providing an overview of the key molecular players involved in NB CSCs and focuses on the experimental evidence from NB cell lines, patient-derived xenografts and primary tumors. It also provides some novel approaches of targeting multiple drivers governing the stemness of CSCs to achieve better anti-tumor effects than the currently used therapeutic agents.
Nervous system tumors represent some of the highly aggressive cancers in both children and adults, particularly neuroblastoma and glioblastoma. Many studies focused on the pathogenic role of the Akt pathway and the mechanistic target of Rapamycin (mTOR) complex in mediating the progression of various types of cancer, which designates the Akt/mTOR signaling pathway as a master regulator for cancer. Current studies are also elucidating the mechanisms of cancer stem cells (CSCs) in replenishing tumors and explicating the strong correlation between the Akt/mTOR pathway and CSC biology. This instigates the development of novel treatments that target CSCs via inhibiting this pathway to prevent recurrence in various cancer subtypes. In accordance, neuroblastoma and glioblastoma tumors are believed to originate from stem/progenitor cells or dedifferentiated mature neural/glial cells transformed into CSCs, which warrants targeting this subpopulation of CSCs in these tumors. In our study, Triciribine and Rapamycin were used to assess the role of inhibiting two different points of the Akt/mTOR pathway in vitro on U251 (glioblastoma) and SH-SY5Y (neuroblastoma) human cell lines and their CSCs. We showed that both drugs minimally decrease the survival of U251 and SH-SY5Y cells in a 2D model, while this effect was much more pronounced in a 3D culture model. Triciribine and Rapamycin decreased migratory abilities of both cell lines and decreased their sphere-forming units (SFU) by extinguishing their CSC populations. Together, we concluded that Rapamycin and Triciribine proved to be effective in the in vitro treatment of glioblastoma and neuroblastoma, by targeting their CSC population.
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Stem cells are undifferentiated cells with the ability to proliferate and convert to different types of differentiated cells that make up the various tissues and organs in the body. They exist both in embryos as pluripotent stem cells that can differentiate into the three germ layers and as multipotent or unipotent stem cells in adult tissues to aid in repair and homeostasis. Perturbations in these cells’ normal functions can give rise to a wide variety of diseases. In this review, we discuss the origin of different stem cell types, their properties and characteristics, their role in tissue homeostasis, current research, and their potential applications in various life-threatening diseases. We focus on neural stem cells, their role in neurogenesis and how they can be exploited to treat diseases of the brain including neurodegenerative diseases and cancer. Next, we explore current research in induced pluripotent stem cell (iPSC) techniques and their clinical applications in regenerative and personalized medicine. Lastly, we tackle a special type of stem cells called cancer stem cells (CSCs) and how they can be responsible for therapy resistance and tumor recurrence and explore ways to target them.
Introduction: The anterior ethmoidal artery (AEA) flap has been demonstrated to be a reliable option for endoscopic repair of symptomatic nasal septal perforations. The purpose of this study is to study the outcome of this technique. Methods: A retrospective case series of all consecutive patients who underwent repair of nasal septal perforation utilizing the AEA flap among 2 institutions from August 2020 to July of 2022 was conducted. Demographics and comorbidities were collected preoperatively and postoperatively. The main outcome of this study was to identify the risk factors for surgical failure. Results: Forty-one patients were included. Mean perforation size was 2.2 cm (range 0.5-4.5 cm). Mean age was 42.5 years (range 14-65 years), 53.6% were female, 39% were active smokers, mean body-mass-index (BMI) was 31.9 (range 19.1-45.5), 20% with history of CRS and 31.7% had diabetes mellitus (DM). Etiologies of the perforation included idiopathic (n = 12), iatrogenic (n = 13), intranasal drug use (n = 7), trauma (n = 6), and secondary to tumor resection (n = 3). Overall success rate for complete closure was 73.2%. Active smoking, history of intranasal drug use, and DM were significantly associated with surgical failure (72.7%vs 26.7%, P = .007; 36.4%vs 10%, P = .047; and 63.6%vs 20%, P = .008 respectively). Conclusion: The endoscopic AEA flap is a reliable technique for closure of nasal septal perforation. It may not work when the etiology is intranasal drug use. Close attention to diabetes and smoking status is also needed.
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