Quantitative analysis of associations between DNA hypermethylation, hypomethylation, and DNMT RNA levels in ovarian tumors.

How hypermethylation and hypomethylation of different parts of the genome in cancer are related to each other and to DNA methyltransferase (DNMT) gene expression is ill defined. We used ovarian epithelial tumors of different malignant potential to look for associations between 5'-gene region or promoter hypermethylation, satellite, or global DNA hypomethylation, and RNA levels for ten DNMT isoforms. In the quantitative MethyLight assay, six of the 55 examined gene loci (LTB4R, MTHFR, CDH13, PGR, CDH1, and IGSF4) were significantly hypermethylated relative to the degree of malignancy (after adjustment for multiple comparisons; P < 0.001). Importantly, hypermethylation of these genes was associated with degree of malignancy independently of the association of satellite or global DNA hypomethylation with degree of malignancy. Cancer-related increases in methylation of only two studied genes, LTB4R and MTHFR, which were appreciably methylated even in control tissues, were associated with DNMT1 RNA levels. Cancer-linked satellite DNA hypomethylation was independent of RNA levels for all DNMT3B isoforms, despite the ICF syndrome-linked DNMT3B deficiency causing juxtacentromeric satellite DNA hypomethylation. Our results suggest that there is not a simple association of gene hypermethylation in cancer with altered DNMT RNA levels, and that this hypermethylation is neither the result nor the cause of satellite and global DNA hypomethylation.

[Study on thyroid defunctionalization method for the preoperative preparation of hyperthyroid operation].

OBJECTIVE: To set up and publicize the thyroid defunctionalization method for the preoperative preparation of hyperthyroid operation. METHODS: 476 hyperthyroid patients admitted in our hospital from March 1990 to February 2005 were studied by groups. They were divided randomly into a test group (244 patients), in which "preoperative preparation method of sequential thyroid defunctionalization" was applied to hyperthyroid patients, and based on the different drug dosages and treating terms used, further 4 subgroups (A, B, C and D) were divided to observe the treatment efficiency; And a control group (232 patients), in which antithyroid drugs and iodine preparation were applied preoperatively to cases. Thyroid functions in every stage of treatment were tested by radioimmunoassays (RIA), and operative bleeding volumes and postoperative complications were observed. RESULTS: Compared to the control group, the thyroid congestion and surface varices were alleviated in the test groups, in which the thyroid tissue of subgroup A most closed to euthyroidism histologically. The mean operative bleeding volume of test group was less than that of the control group. The bleeding volumes were (324.76 +/- 163.26) mL for the control group, (195.74 +/- 57.07) mL for the subgroup A, (230.00 +/- 70.81) mL for the subgroup B, (240.47 +/- 80.29) mL for the subgroup C and (314.75 +/- 96.46) mL for the subgroup D. There was no significant difference between the control group and subgroup D, but compared with the subgroup A, B, and C, there was the significant difference between control and treated subgroup (P < 0.05). The postoperative complication rate of the test group was 8.61% (21/244), while that of the control group was 17.24 (40/232). There was statistic difference between two groups (P < 0.005). CONCLUSION: The key to "preoperative preparation method of sequential thyroid defunctionalization" is as follows: the synthesis of thyroxin should be fully inhibited to thyroid defunctionalized; sufficient exogenous thyroxin should be supplemented; the term of thyroid function compensation should be long enough. The "preoperative preparation method of sequential thyroid defunctionalization" can decrease perioperational complications effectively and operation risks.