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At least 541 records · Page 30Linked to original sources
PubMed2004

Quinoxaline 1,4-dioxides are novel angiogenesis inhibitors that potentiate antitumor effects of ionizing radiation.

We have recently shown that quinoxaline 1,4-dioxides (QdNOs) are potent hypoxia selective cytotoxins that modulate hypoxia inducible factor-1alpha (HIF-1alpha) expression. In this study, we evaluated the cytotoxicity, anti-angiogenic, and radiosensitization activities of the two quinoxaline 1,4-dioxides (QdNOs), BPQ and DCQ. Clonogenic survival, Matrigel, and radiosensitization assays were performed in vitro and in vivo using Lewis lung carcinoma (LLC) and EMT-6 mammary adenocarcinoma cells. Transcript and protein levels of HIF-1alpha and VEGF were determined using RT-PCR and Western blotting, respectively. DCQ showed cytotoxic effects under hypoxic conditions for both cell lines. Treatment with either drug inhibited HIF-1alpha and VEGF secretion, with DCQ being more potent than BPQ. DCQ also inhibited the formation of tube-like structures of ECV-304 endothelial cells in Matrigel by 60-80% and significantly reduced neoangiogenesis in vivo. When combined with radiation (200-1000 cGy), DCQ resulted in the death of 100% of LLC or EMT-6 cells. Using the C57BL/6 mouse model, combined treatment with DCQ and radiation delayed the growth of LLC tumors for 17 days and reduced mean tumor volume by 80% at day 20. However, BPQ combined with radiation did not induce significant tumor regression. Histological analyses revealed a significant increase in tissue necrosis in tumors treated by DCQ and radiation. These results indicate a potent anti-angiogenic and radiation modification effect of two quinoxaline dioxides. These findings should stimulate further research in other tumor models as these compounds could have potential clinical applications in cancer therapy.

Adenocarcinoma↗
PubMedDate not supplied

[Using aphobazol for treatment of the emotional stress after exposure to ionizing radiation].

Emotional stress after radiation may aggravate the course of radiation-induced diseases. The use of the selective anxiolytic aphobazol (a drug from a mercaptobenzamidasol group) corrects development of adaptive reactions to stress in the blood system and normalizes its compensatory potentialities in animals under conditions of combined influence of intensive long-term emotional stress and low-dose irradiation. In lethally irradiated animals the treatment of stressed animals with aphobazol favourably influenced the course of acute radiation disease, enhanced recovery processes in the blood system, increased the animals' survival. The use of aphobazol completely removed a negative effect of emotional stress in indralin-protected animals. Thus, pharmacological correction of the emotional stress caused by different doses of radiation is not only a symptomatic but also a pathogenetically justified form of treatment.

Adaptation, Physiological↗
PubMed1991

Interaction between ionizing radiation and supercoiled DNA within human tumor cells.

We have analyzed DNA supercoiling within histone-free nuclei (nucleoids) using four human squamous cell carcinoma cell lines that express varying degrees of radiosensitivity. The entire DNA, arranged as negative supercoiled loops attached to the nuclear matrix, was extracted from single cells, stained with ethidium bromide, and passed through a flow cytometer recording both light scatter and red (DNA) fluorescence. Supercoiled loops of DNA from all cells were unwound with a low concentration of ethidium bromide, as seen by increased light scatter. Nucleoids from radiosensitive but not radioresistant cells resisted the transition from zero to positive supercoiling at higher concentrations of ethidium bromide. The profile of red DNA fluorescence from ethidium bromide-stained nucleoids showed that the radiosensitive cells expressed a greater variation in the total amount of ethidium bromide bound. After 12 Gy of gamma-radiation, radiosensitive cell lines produced nucleoids that contained a greater proportion of relaxed supercoiled DNA, making them larger than those from radioresistant cell lines. We suggest these observations are secondary effects resulting from an altered affinity between supercoiled looped DNA and the nuclear matrix. Combined with radiation damage, these structural alterations may lead to a more complex type of damage to repair within the radiosensitive cell lines.

Carcinoma, Squamous Cell↗
PubMed1986

[Modification of separate and combined effects of hyperthermia and ionizing radiation on normal tissues].

In experiments on mice a study was made of the influence of serotonin, glucose, 5-FU, actinomycin D, cycloheximide, metronidazole, ethanol, novocaine, and a hypoxic gaseous mixture on the severity of skin injuries in separate and combined use of gamma-beam radiation and hyperthermia. Some agents were shown to be able to modify thermo- and radiosensitivity of tissues, in some cases the directions of changes did not coincide (i.e. sensitization to one of the injuring agents and protection by the other). In most cases the modifier summary effect in thermo- and radiotherapeutic exposure of the skin did not result in additive change of heating and irradiation. It suggested that the use of radiation modifiers in thermo- and radiotherapeutic exposure required a thorough study of the effect in each specific variant of the combination of agents.

Animals↗