PLK1 blockade enhances therapeutic effects of radiation by inducing cell cycle arrest at the mitotic phase

The cytotoxicity of ionizing radiation depends on the cell cycle phase; therefore, its pharmacological manipulation, especially the induction of cell cycle arrest at the radiosensitive mitotic-phase (M-phase), has been attempted for effective radiation therapy. Polo-like kinase 1 (PLK1) is a serine/threonine kinase that functions in mitotic progression, and is now recognized as a potential target for radiosensitization. We herein investigated whether PLK1 blockade enhanced the cytotoxic effects of radiation by modulating cell cycle phases of cancer cells using the novel small molecule inhibitor of PLK1, TAK-960. The TAK-960 treatment exhibited radiosensitizing effects in vitro, especially when it increased the proportion of M-phase cells. TAK-960 did not sensitize cancer cells to radiation when an insufficient amount of time was provided to induce mitotic arrest. The overexpression of a PLK1 mutant, PLK1-R136G&T210D, which was confirmed to cancel the TAK-960-mediated increase in the proportion of mitotic cells, abrogated the radiosensitizing effects of TAK-960. A tumor growth delay assay also demonstrated that the radiosensitizing effects of TAK-960 depended on an increase in the proportion of M-phase cells. These results provide a rational basis for targeting PLK1 for radiosensitization when considering the therapeutic time window for M-phase arrest as the best timing for radiation treatments

The eigenvalue problem for infinite compact complex symmetric matrices with application to the numerical computation of complex zeros of J0(z) − iJ1(z) and of Bessel functions Jm(z) of any real order m

AbstractConsider computing simple eigenvalues of a given compact infinite matrix re- garded as operating in the complex Hilbert space l2 by computing the eigenvalues of the truncated finite matrices and taking an obvious limit. In this paper we deal with a special case where the given matrix is compact, complex, and symmetric (but not necessarily Hermitian). Two examples of application are studied. The first is con- cerned with the equation J0(z) − iJ1(z)=0 appearing in the analysis of the solitary-wave runup on a sloping beach, and the second with the zeros of the Bessel function Jm(z) of any real order m. In each case, the problem is reformulated as an eigenvalue problem for a compact complex symmetric tridiagonal matrix operator in l2 whose eigenvalues are all simple. A complete error analysis for the numerical solution by truncation is given, based on the general theorems proved in this paper, where the usefulness of the seldom used generalized Rayleigh quotient is demonstrated

Free Amino Acids and Related Compounds in the Fluid from Surgical Ciliated Cysts of the Maxilla

Fluids from 6 surgical ciliated cysts of the maxilla and autologous sera were analyzed for total free amino acids and related compounds concentrations. All of the amino acids present in the serum were observed in the cyst fluids, but the concentrations and profile of their constituents were markedly different from that of the serum. The concentrations of non-essential amino acids such as Ala, Glx, and Gly were extremely low in the cyst fluids. The composition and concentration of the amino acids and related compounds in the fluids of these cysts may reflect the balance between proteolytic and catabolic metabolism and also in the permeability effect of the lining cells of the cyst wall