Unusual cis-diprotonated forms and fluorescent aggregates of non-peripherally alkoxy-substituted metallophthalocyanines.

Protonation and aggregation of two metallophthalocyanines (zinc and magnesium) non-peripherally substituted with 1,4,7-trioxanonyl moieties were studied by steady-state and time-resolved optical spectroscopy. Both compounds are easily protonated in organic solvents, but the central metal ion strongly affects the character of this process. In particular, the magnesium derivative forms the cis-diprotonated isomer observed for the first time in phthalocyanines, in contrast to its zinc counterpart which forms the typical trans-diprotonated isomer. In addition, studies performed on phthalocyanines substituted with n-butoxy groups at their non-peripheral positions indicated that the formation of the cis-diprotonated forms is a more common feature of alkoxy-substituted magnesium metallophthalocyanines, in contrast to derivatives with other metal ions. The cis-diprotonated forms of the magnesium derivatives are formed at much lower proton concentrations than the trans-diprotonated forms of their zinc counterparts. The cis-isomers were also found to have more advantageous photophysical properties for photoactive applications than the trans-isomers. Aggregation studies of the trioxanonyl phthalocyanines revealed that the magnesium derivative aggregates much more easily in non-coordinating solvents than its zinc counterpart. Both the derivatives form fluorescent aggregates, which is typically attributed to the presence of oxygen-to-metal intermolecular coordination preventing the formation of non-fluorescent face-to-face stacks. The results indicate that the oxygen-to-metal coordination plays a significant role in the studied systems and the stronger oxygen-coordination ability of magnesium ions compared to zinc ions may underlie the observed differences between the phthalocyanines metallated with these two ions.

Effect of resveratrol analogue, DMU-212, on antioxidant status and apoptosis-related genes in rat model of hepatocarcinogenesis.

The aim of the study was to examine whether antioxidant properties of 3,4,4',5-tetramethoxystilbene (DMU-212) contribute to its anticarcinogenic activity and whether DMU-212 affects the expression of apoptosis-related genes. Two-stage model of hepatocarcinogenesis was used; male Wistar rats were challenged with N-nitrosodiethylamine (NDEA), 200 mg/kg body weight (b.w.), intraperitoneal, then phenobarbital (PB) in drinking water (0.05%) was administered. Simultaneously, DMU-212 was given per os at a dose 20 or 50 mg/kg b.w. two times a week for 16 weeks. DMU-212 caused a moderate decrease in hepatic thiobarbituric acid reactive substances and protein carbonyls concentration elevated in rats treated with NDEA/PB. The activity of antioxidant enzymes examined reduced by NDEA/PB treatment was not restored in rats coadministered with DMU-212. Effects of DMU-212 on messenger RNA (mRNA) expression of antioxidant enzymes in rats challenged with NDEA/PB were diversified; no changes in their protein expression were noted in any of the groups. The expression of 17,000 genes was analyzed by Affymetrix® Rat Gene 1.1 ST Array; 15 apoptosis-related genes were selected and validated by RT-q PCR. The combined treatment with NDEA/PB and DMU-212 increased the mRNA level of some genes driving mitochondria-mediated apoptosis, whereas the mRNA expression of some anti-apoptotic genes triggering receptor-mediated apoptosis was reduced. The expression of genes encoding caspases-4, -8, -9, and -12 was also increased in rats treated with DMU-212. Although antioxidant effect of DMU-212 in rats challenged with NDEA/PB was moderate, its potential anticarcinogenic properties were demonstrated as evidenced by modulation of apoptosis-related genes.

A prospective, randomised study to compare two palliative radiotherapy schedules for non-small-cell lung cancer (NSCLC).

A prospective randomised study compared two palliative radiotherapy schedules for inoperable symptomatic non-small-cell lung cancer (NSCLC). After stratification, 100 patients were randomly assigned to 20 Gy/5 fractions (fr)/5 days (arm A) or 16 Gy/2 fr/day 1 and 8 (arm B). There were 90 men and 10 women aged 47-81 years (mean 66), performance status 1-4 (median 2). The major clinical characteristics and incidence and degree of initial disease-related symptoms were similar in both groups. Treatment effects were assessed using patient's chart, doctor's scoring of symptomatic change and chest X-ray. Study end points included degree and duration of symptomatic relief, treatment side effects, objective response rates and overall survival. A total of 55 patients were assigned to arm A and 45 to arm B. In all, 98 patients received assigned treatment, whereas two patients died before its termination. Treatment tolerance was good and did not differ between study arms. No significant differences between study arms were observed in the degree of relief of all analysed symptoms. Overall survival time differed significantly in favour of arm B (median 8.0 vs 5.3 months; P=0.016). Both irradiation schedules provided comparable, effective palliation of tumour-related symptoms. The improved overall survival and treatment convenience of 2-fraction schedule suggest its usefulness in the routine management of symptomatic inoperable NSCLC.