Factors influencing overall survival rates for patients with pineocytoma

Given its rarity, appropriate treatment for pineocytoma remains variable. As the literature primarily contains case reports or studies involving a small series of patients, prognostic factors following treatment of pineocytoma remain unclear. We therefore compiled a systematic review of the literature concerning post-treatment outcomes for pineocytoma to better determine factors associated with overall survival among patients with pineocytoma. We performed a comprehensive search of the published English language literature to identify studies containing outcome data for patients undergoing treatment for pineocytoma. Kaplan–Meier analysis was utilized to determine overall survival rates. Our systematic review identified 168 total patients reported in 64 articles. Among these patients, 21% underwent biopsy, 38% underwent subtotal resection, 42% underwent gross total resection, and 29% underwent radiation therapy, either as mono- or adjuvant therapy. The 1 and 5 year overall survival rates for patients receiving gross total resection versus subtotal resection plus radiotherapy were 91 versus 88%, and 84 versus 17%, respectively. When compared to subtotal resection alone, subtotal resection plus radiation therapy did not offer a significant improvement in overall survival. Gross total resection is the most appropriate treatment for pineocytoma. The potential benefit of conventional radiotherapy for the treatment of these lesions is unproven, and little evidence supports its use at present

Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid

Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain

Abstracts from the 20th International Symposium on Signal Transduction at the Blood-Brain Barriers

https://deepblue.lib.umich.edu/bitstream/2027.42/138963/1/12987_2017_Article_71.pd

Using Acetaminophen's Toxicity Mechanism to Enhance Cisplatin Efficacy in Hepatocarcinoma and Hepatoblastoma Cell Lines

Background/Aims: Acetaminophen overdose causes hepatotoxicity mediated by toxic metabolites generated through the cytochrome P450 enzyme. The objective of this study was to investigate whether acetaminophen (AAP) can enhance cisplatin (CDDP) cytotoxicity against human hepatocarcinoma and hepatoblastoma cells in vitro and whether this effect can be prevented by N-acetylcysteine (NAC). Methods: In vitro studies (glutathione [GSH] level, cell viability, and immunoblot assays) were performed using human hepatocarcinoma and hepatoblastoma cells cultured in AAP, CDDP, and the combination of both with or without delayed NAC administration. The pharmacology and toxicology of high-dose AAP in rats were also examined. Results: Acetaminophen decreased GSH levels in liver cancer cells in a dose- and time-dependent manner. Acetaminophen combined with CDDP had enhanced cytotoxicity over CDDP alone. The cytotoxicity caused by AAP plus CDDP was decreased by NAC, with the effectiveness being time-dependent. The GSH level was lowered in the liver but not in the blood or the brain in rats treated with a high dose of AAP (1000 mg/kg). The expression of CYP2E1 protein, a key cytochrome P450 enzyme, varies among species but is not correlated to AAP sensitivity in liver cancer cells. Conclusions: Our results suggest that a chemotherapeutic regimen containing both AAP and CDDP with delayed NAC rescue has the potential to enhance chemotherapeutic efficacy while decreasing adverse effects. This would be a promising approach particularly for hepatoblastomas regardless of cellular CYP2E1 protein level but could also be beneficial in other malignancies