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Kostin P.A.,Karpov Institute of Physical Chemistry | Zakarzhevskaya N.B.,Karpov Institute of Physical Chemistry | Generozov E.V.,Karpov Institute of Physical Chemistry | Govorun V.M.,Karpov Institute of Physical Chemistry | Shelygin Yu.A.,State Center for Research in Coloproctology
Voprosy Onkologii | Year: 2010

Sequential treatment of bisulfate-converted DNA was used to study methylation of promoter areas of SEPT9, HLTF, ALX4 and CDH1 genes. Methylation profiles were evaluated by comparing bioptical findings on colorectal cancer (n=55) and morphologically intact areas of the large bowel (n=71). Significant differences between groups were established for SEPT9, HLTF and ALX4 genes (p≤10-9) in evaluating medium-rate methylation of CpG. Diagnostic sensitivity (Se) peaked for SEPT9 (78±7%); specificity - (86±4%) (Sp). On site CpG (position «+14»), similar findings were reported: Se=81±6%, Sp=77±5%. Therefore, CpG14 SEPT9 may be used as a separate marker. As a result of the use of HLTF as marker on all 23 sites, Se was 67±6% and Sp - 87±3%; ALX4 diagnostic sensitivity - 59±6%. Specificity level was similar to those of the other genes (88±3%). Despite the role of CDH1 gene in colorectal cancer, the group-to-group differences in methylation rates were minimal. Such values of Se and Sp as 54±6% and 67±5%, respectively, could not support methylation of the CDH1 promoter area for diagnostic purposes. Therefore, combined evaluation of SEPT9, HLTF and ALX4 genes offered more advantage as far as diagnosis is concerned. Hypermethylation in two of the three genes was assumed as a criterion for diagnosis. Under such conditions, diagnostic sensitivity was 81±7% (Sp=93±3%). With such high values, the criterion has a potential of being instrumental in working out diagnostic tests for colorectal cancer.

Shelygin Yu.A.,State Center for Research in Coloproctology | Alexeev M.V.,State Center for Research in Coloproctology | Rybakov Ye.G.,State Center for Research in Coloproctology | Pankratova A.A.,Pa Herzen Research Institute Of Oncology | Plyutinskaya A.D.,Pa Herzen Research Institute Of Oncology
Voprosy Onkologii | Year: 2010

Previously, significant increase in survival in locally-advanced rectal cancer as a result of heated intraoperative intraperitoneal chemotherapy was reported. Our study used cisplatin 0.5mg/ml (0.05 per cent solution) in the culture of pharyngeal epidermoid carcinoma (PEC) cells (HEP-2) and A-549 culture of lung carcinoma cells. The number of viable cells was estimated colorimetrically after 24 and 48 hr incubation. 50%-rise in inhibition of culture growth was assumed to be biologically significant. Forty-eight hours after inoculation, single dose of cisplatin 8mg/kg was injected in mice bearing transplanted lung carcinoma of Lewis (LLC). That was followed by death of tumor cells. Preheating (45 deg. C, 1hr) did not influence either the cytostatic or therapeutic effect of cisplatin in vivo. That procedure inhibited tumor growth by 7-8% and the effect did not wear off until day 11or longer. Survival in LLC-bearing mice rose by 26% which pointed to the advantages offered by heated cytostatic chemotherapy.

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