Role of p53 mutation in the effect of boron neutron capture therapy on oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Boron neutron capture therapy (BNCT) is a selective radiotherapy, being effective for the treatment of even advanced malignancies in head and neck regions as well as brain tumors and skin melanomas. To clarify the role of p53 gene, the effect of BNCT on oral squamous cell carcinoma (SCC) cells showing either wild- (SAS/neo) or mutant-type (SAS/mp53) p53 was examined.</p> <p>Methods</p> <p>Cells were exposed to neutron beams in the presence of boronophenylalanine (BPA) at Kyoto University Research Reactor. Treated cells were monitored for modulations in colony formation, proliferation, cell cycle, and expression of cell cycle-associated proteins.</p> <p>Results</p> <p>When SAS/neo and SAS/mp53 cells were subjected to BNCT, more suppressive effects on colony formation and cell viability were observed in SAS/neo compared with SAS/mp53 cells. Cell cycle arrest at the G1 checkpoint was observed in SAS/neo, but not in SAS/mp53. Apoptotic cells increased from 6 h after BNCT in SAS/neo and 48 h in SAS/mp53 cells. The expression of p21 was induced in SAS/neo only, but G2 arrest-associated proteins including Wee1, cdc2, and cyclin B1 were altered in both cell lines.</p> <p>Conclusion</p> <p>These results indicate that oral SCC cells with mutant-type are more resistant to BNCT than those with wild-type p53, and that the lack of G1 arrest and related apoptosis may contribute to the resistance. At a physical dose affecting the cell cycle, BNCT inhibits oral SCC cells in p53-dependent and -independent manners.</p

Jasmonate-dependent plant defense restricts thrips performance and preference

<p>Abstract</p> <p>Background</p> <p>The western flower thrips (<it>Frankliniella occidentalis </it>[Pergande]) is one of the most important insect herbivores of cultivated plants. However, no pesticide provides complete control of this species, and insecticide resistance has emerged around the world. We previously reported the important role of jasmonate (JA) in the plant's immediate response to thrips feeding by using an <it>Arabidopsis </it>leaf disc system. In this study, as the first step toward practical use of JA in thrips control, we analyzed the effect of JA-regulated <it>Arabidopsis </it>defense at the whole plant level on thrips behavior and life cycle at the population level over an extended period. We also studied the effectiveness of JA-regulated plant defense on thrips damage in Chinese cabbage (<it>Brassica rapa </it>subsp. <it>pekinensis</it>).</p> <p>Results</p> <p>Thrips oviposited more on <it>Arabidopsis </it>JA-insensitive <it>coi1-1 </it>mutants than on WT plants, and the population density of the following thrips generation increased on <it>coi1-1 </it>mutants. Moreover, thrips preferred <it>coi1-1 </it>mutants more than WT plants. Application of JA to WT plants before thrips attack decreased the thrips population. To analyze these important functions of JA in a brassica crop plant, we analyzed the expression of marker genes for JA response in <it>B. rapa</it>. Thrips feeding induced expression of these marker genes and significantly increased the JA content in <it>B. rapa</it>. Application of JA to <it>B. rapa </it>enhanced plant resistance to thrips, restricted oviposition, and reduced the population density of the following generation.</p> <p>Conclusion</p> <p>Our results indicate that the JA-regulated plant defense restricts thrips performance and preference, and plays an important role in the resistance of <it>Arabidopsis </it>and <it>B. rapa </it>to thrips damage.</p

Markedly improved outcomes and acceptable toxicity in adolescents and young adults with acute lymphoblastic leukemia following treatment with a pediatric protocol: a phase II study by the Japan Adult Leukemia Study Group

The superiority of the pediatric protocol for adolescents with acute lymphoblastic leukemia (ALL) has already been demonstrated, however, its efficacy in young adults remains unclear. The ALL202-U protocol was conducted to examine the efficacy and feasibility of a pediatric protocol in adolescents and young adults (AYAs) with BCR\u27ABL-negative ALL. Patients aged 15\u2724 years (n = 139) were treated with the same protocol used for pediatric B-ALL. The primary objective of this study was to assess the disease-free survival (DFS) rate and its secondary aims were to assess toxicity, the complete remission (CR) rate and the overall survival (OS) rate. The CR rate was 94%. The 5-year DFS and OS rates were 67% (95% confidence interval (CI) 58\u2775%) and 73% (95% CI 64\u2780%), respectively. Severe adverse events were observed at a frequency that was similar to or lower than that in children treated with the same protocol. Only insufficient maintenance therapy significantly worsened the DFS (hazard ratio 5.60, Po0.001).These results indicate that this protocol may be a feasible and highly effective treatment for AYA with BCR\u27ABL-negative ALL