Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.21 (CPT)
 4,580 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The theoretical background of the present investigation was the decoupling hypothesis of alexithymia, which presumes for alexithymic individuals a dissociation of psychophysiological indicators of emotion from verbal cognitive awareness of one's emotional state. To study alterations in reactivity to emotionally distressing stimuli in alexithymic individuals, 12 high-alexithymic and 14 low-alexithymic subjects (separated by TAS) out of a general sample of 54 were investigated. All subjects were exposed to cognitive (CPT) and affect inductive (film sequences) distress. During stimulus exposition electrodermal activity (spontaneous fluctuations) was recorded. After stimulus exposition the subjects assessed their emotional reaction towards the film sequences (DAS). Concerning electrodermal activity no differences were found between high and low alexithymics under cognitive distress. In any case a significant autonomous arousal was registered. However, only the low alexithymic subjects but not the high alexithymics showed a significant increase of spontaneous fluctuations as expression of autonomous arousal during presentation of affect inductive stimuli. The altered psychophysiological reactivity found in high alexithymics in contrast to low alexithymic subjects was revealed specifically for the processing of emotional qualified stimuli. However, there was no difference between the groups in cognitive self assessment of emotional response towards the film sequences. The findings are discussed with reference to neurophysiological and psychodynamic models and the decoupling hypothesis of alexithymia.
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PMID:[Feelings without speech or speech without feelings? Further evidence for the decoupling hypothesis of alexithymia]. 1023 8

TAS-103 is a novel anticancer agent targeting both topoisomerase (Topo) I and Topo II, that stabilizes cleavable complexes of Topo-DNA at the cellular level. In this study, the in vitro antitumor effects of TAS-103 were compared with those of other known Topo I and Topo II inhibitors. TAS-103 inhibited DNA synthesis more strongly than RNA and protein synthesis, and induced an increase of cell population in the S-G2/M phase. The cytotoxicity of TAS-103 was strongest against S-phase cells, but its cell cycle phase specificity was not clear, and depended on drug concentration and exposure time. The cytotoxicity of TAS-103 (IC50: 0.0030-0.23 microM) against various tumor cell lines was much stronger than that of VP-16 and comparable to that of SN-38. The cytotoxicity of TAS-103 seemed to be more related to the amount of protein-DNA complexes than to the accumulation of TAS-103 in the cells. P-Glycoprotein (P-gp)-mediated MDR, CDDP-resistant and 5-FU-resistant cell lines did not show cross-resistance to TAS-103. Although PC-7/CPT cells bearing a Topo I gene mutation showed cross-resistance to TAS-103, the sensitivity of P388/CPT, HT-29/CPT and St-4/CPT cells, showing decreased Topo I expression, was not changed. KB/VM4 and HT-29/Etp cells, showing decreased Topo II expression, were slightly cross-resistant to TAS-103. These results suggest that TAS-103 may act as an inhibitor of both Topo I and Topo II at the cellular level. This property may be responsible for its strong antitumor effect and broad-spectrum, growth-inhibitory effect on drug-resistant cell lines.
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PMID:In vitro antitumor activity of TAS-103, a novel quinoline derivative that targets topoisomerases I and II. 1039 Oct 99