Medullary thyroid carcinoma (MTC) occurs as a sporadic tumor or in connection with inherited cancer syndromes of multiple endocrine neoplasia type 2 and familial MTC. Missense RET proto-oncogene mutations and small in-frame deletions are found in most of the cases. In a significant amount of sporadic MTC cases somatic mutation at codon 918 (exon 16), or at codons 609, 611, 618, 620 (exon 10), or codons 630, 634 (exon 11) appear. We report here on three new somatic cell missense mutations of the RET proto-oncogene associated with sporadic MTC. In one tumor mutation at codon 922 TCC(Ser)-->TTC(Phe) in exon 16 was found. In another tumor two mutations at codons 639 GCA(Ala)-->GGA(Gly) and 641 GCT(Ala)-->CGT(Arg) in the exon 11 were observed. Allele-specific PCR followed by sequencing demonstrated the presence of both mutations at the same allele.

В обзоре приведены современные данные об основных патогенетических механизмах, обусловливающих неконтролируемый рост и метастазирование опухоли, развитие ее резистентности к традиционным методам терапии. Генетическая нестабильность клетки, связанная с накоплением мутаций в генах контроля клеточного роста и дифференцировки, является ключевым моментом опухолевой прогрессии. Понимание и детальное изучение процессов канцерогенеза лежит в основе создания новых противоопухолевых препаратов, что, в свою очередь, позволяет оптимизировать и индивидуализировать лечение пациентов с онкологическими заболеваниями.

The effects of beta‐carotene, vitamin E and a pharmaceutical complex of natural anti‐oxidants (OXY‐GARD) on abnormally high ornithine decarboxylase (ODC) activity in antral gastric mucosa of patients with atrophic gastritis (AG), accompanied by intestinal metaplasia (IM), were studied in a randomized placebo‐controlled clinical trial. In cases with H. pylori infection, preliminary eradication of this bacterium was carried out utilizing a standard chemotherapeutic schedule (de nol+metronidazole+oxytetracycline). Efficient eradication of H. pylori resulted in an ODC activity decrease of 16%, on average. It was shown that supplementation with beta‐carotene, at a daily dose of 20 mg, or with vitamin E, at a daily dose of 400 IU, produced decreases in ODC activity of 46% and 44%, respectively, by three months. Daily supplementation with 1 or 2 capsules of OXY‐GARD for three months resulted in ODC activity decreases of 23% and 48%, respectively. Taking into account that abnormally high ODC activity is associated with a high oncogenic potential and plays a specific role in tumor promotion, it is reasonable to suggest that beta‐carotene, vitamin E and OXY‐GARD act in atrophic or premalignant gastric mucosa as anti‐promoters. Preliminary data indicate that prolonged administration of these nutritional supplements, e.g. beta‐carotene for one year, to IM patients produces the maximum decrease in ODC activity at three months. We found that this decrease was accompanied by a delayed partial regression of IM in nine of 18 patients (response rate 50%, 95% confidence interval 26–74%). A study on the effects of long‐term vitamin E or OXY‐GARD supplementation on IM regression is currently in progress. (Dig Endosc 1996 ; 8 : 184–191)

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