Age as a decisive factor in general anaesthesia use in paediatric proton beam therapy.

Proton therapy for paediatric cancer patients is an effective treatment; however, young children have may have difficulties staying still during irradiation. This study investigated the indication of general anaesthesia in paediatric proton therapy. Background information and anaesthesia/treatment protocols were retrospectively extracted from the medical records of cancer patients under 15 years who underwent proton therapy at Southern TOHOKU General Hospital, Fukushima, Japan between April 2016 and December 2018. The anaesthesia and non-anaesthesia groups were compared to evaluate factors determining the need for general anaesthesia. Thirty-two patients who received 285 irradiations were analysed. The median age was 5 years old (range: 1-15), and 13 patients (40.6%) were female. Twelve (37.5%) patients received general anaesthesia. In the general anaesthesia group, airway management using a laryngeal mask was performed in 11 patients (91.6%). Patient age was significantly lower in the general anaesthesia group than in the non-anaesthetised group (p < 0.001). Considering all background factors, only age was strongly associated with anaesthesia in the univariate logistic regression model (odds ratio 0.55 [95% confidence interval 0.35-0.86]; P < 0.01). Thus, age is one of the most important factors determining the need for general anaesthesia during proton therapy in children.

Expression of cystatin C prevents oxidative stress-induced death in PC12 cells.

Cystatin C, an inhibitor of cysteine proteinases, is suggested to be involved in oxidative stress-induced apoptosis of cultured CNS neurons and various neuronal diseases in vivo; however, little is known about its mechanism of action. To address the role cystatin C plays in oxidative stress-induced neuronal cell death, we established PC12 cell lines that stably expressed rat cystatin C. These cystatin C-expressing PC12 cells showed remarkable resistance to high (50%) oxygen atmosphere. This resistance correlate with expression levels of cystatin C, demonstrating that cystatin C has a protective effect on high oxygen-induced cell death. In contrast, in a normal (20%) oxygen atmosphere neither control nor cystatin C-expressing PC12 cells showed a significant change in the number of living cells, indicating that cystatin C does not play an important role in the regulation of cellular proliferation. Furthermore, the cystatin C-expressing cell line also resisted other oxidative stresses, including glutamate- and 13-L-hydroperoxylinoleic acid (LOOH)-induced cell death. These results demonstrate that cystatin C has protective effects against various oxidative stresses that induce cell death.

Csk defines the ability of integrin-mediated cell adhesion and migration in human colon cancer cells: implication for a potential role in cancer metastasis.

Progression of human colon cancer is often associated with elevated expression and activity of the Src family tyrosine kinase (SFK). SFK is ordinarily in equilibrium between inactive and primed states by a balance of negative regulatory kinase Csk and its counteracting tyrosine phosphatase(s), both of which act on the regulatory C-terminal tyrosine of SFK. To evaluate the contribution of the regulatory system of SFK in cancer progression, we here modulated the equilibrium status of SFK by introducing wild-type or dominant-negative Csk in human epithelial colon cancer cells, HCT15 and HT29. Overexpression of wild-type Csk induced decreased SFK activation, increased cell-cell contacts mediated by E-cadherin, decreased the number of focal contacts and decreased cell adhesion/migration and in vitro invasiveness. Conversely, expression of a dominant-negative Csk resulted in elevated SFK activation, enhanced phosphorylation of FAK and paxilllin, enhanced cell scattering, an increased number of focal contacts, dramatic rearrangement of actin cytoskeleton and increased cell adhesion/migration and in vitro invasiveness. In these scattered cells, however, localization, expression and phosphorylation of either E-cadherin or beta-catenin were not significantly affected, suggesting that the E-cadherin-mediated cell-cell contact is indirectly regulated by SFK. Furthermore, all these events occurred absolutely dependent on integrin-mediated cell adhesion. These findings demonstrate that Csk defines the ability of integrin-SFK-mediated cell adhesion signaling that influences the metastatic potential of cancer cells.