Unlabelled iododeoxyuridine increases the cytotoxicity and incorporation of [1251]-iododeoxyuridine in two human glioblastoma cell lines

Iododeoxyuridine (IUdR), labelled with radioiodines emitting Auger, alpha or beta- radiation, has been proposed as a therapeutic tool in the treatment of cancer. However, the low per cent incorporation in tumour cells and limited cytotoxicity are major obstacles for such an application. Using unlabelled IUdR as a modulator, we have studied the in vitro cytotoxicity of [125I]-IUdR in two human glioblastoma cell lines. Surprisingly, an enhanced cytotoxicity of [125I]-IUdR was observed in the presence of 0.3-10 microM concentrations of unlabelled IUdR in U251 glioblastoma cells and to a lesser extent in LN229 cells. The presence of unlabelled IUdR unexpectedly increased the incorporation of [125I]-IUdR in both cell lines. Thymidine competitively blocked the cytotoxic effects of combined unlabelled and [125I]-labelled IUdR in these cells and DNA-incorporation of radiolabelled IUdR

Unlabelled iododeoxyuridine increases the rate of uptake of [125I]iododeoxyuridine in human xenografted glioblastomas

5-Iodo-2'-deoxyuridine (IdUrd), a thymidine (TdR) analogue, can be radiolabelled with iodine-125, an Auger radiation emitter, to provoke double-strand breaks once incorporated into DNA of cancer cells. We have previously shown that co-incubation of [125I]IdUrd with unlabelled IdUrd provided an additive cytotoxicity in two human glioblastoma cell lines. This observation was unexpectedly correlated with an increase in the rate of DNA incorporation of [125I]IdUrd. Here, we further evaluated the effects of unlabelled IdUrd on the uptake of [125I]IdUrd in vitro and in vivo in mice xenografted with three human glioblastoma lines. The results showed that, in these three glioblastoma lines, unlabelled IdUrd increased the rate of uptake of [125I]IdUrd in vitro by 2- to 4.4-fold and in vivo by 1.5- to 2.8-fold. The rate of uptake of [125I]IdUrd in normal rapidly dividing tissues was also increased by 1.3- to 2.8-fold. TdR completely blocked [125I]IdUrd uptake in tumours and tissues. Analogues of IdUrd, such as deoxyuridine and 5-iodo-1,3-dimethyuracil, did not reproduce the effect of IdUrd on the uptake of [125I]IdUrd, suggesting that it is not related to protection against [125I]IdUrd degradation. It is concluded that combined administration of unlabelled IdUrd may improve the use of radiolabelled IdUrd for cancer diagnosis or therapy

Digital Signal Processing

Contains research objectives and summary of research on eight research projects and a report on one research project.U.S. Navy Office of Naval Research (Contract N00014-67-A-0204-0064)National Science Foundation (Grant GK-31353

An evaluation of objective measures for intelligibility prediction of time-frequency weighted noisy speech

Existing objective speech-intelligibility measures are suitable for several types of degradation, however, it turns out that they are less appropriate in cases where noisy speech is processed by a time-frequency weighting. To this end, an extensive evaluation is presented of objective measure for intelligibility prediction of noisy speech processed with a technique called ideal time frequency (TF) segregation. In total 17 measures are evaluated, including four advanced speech-intelligibility measures (CSII, CSTI, NSEC, DAU), the advanced speech-quality measure (PESQ), and several frame-based measures (e.g., SSNR). Furthermore, several additional measures are proposed. The study comprised a total number of 168 different TF-weightings, including unprocessed noisy speech. Out of all measures, the proposed frame-based measure MCC gave the best results (q¼0.93). An additional experiment shows that the good performing measures in this study also show high correlation with the intelligibility of single-channel noise reduced speech.MediamaticsElectrical Engineering, Mathematics and Computer Scienc