Thus, insulin resistance/hyperinsulinemia is associated with a more aggressive course of the disease in certain groups of the patients but--in contrast to excessive estrogenic stimulation--does not result in increased genotoxic damage in tumor and normal tissues. The data obtained once more confirm the need for treatment and prevention measures aimed at correcting hormonal-metabolic disturbances in endometrial cancer patients and groups at risk of this disease. Such an approach might include use of antidiabetic biguanides, thiazolidinediones (glitazones), and statins.
Objectives: To compare estrogen concentrations in endometrial cancer tissue with those in macroscopically normal endometrium and with certain morphological characteristics of the tumor and endocrine parameters in patients. Methods: The estradiol content was evaluated by radioimmunoassay after homogenization and extraction in 78 adenocarcinomas (61 from postmenopausal patients). Results: Higher concentrations of estradiol in tumor tissue samples than in macroscopically normal endometrium were found in patients of both reproductive and postmenopausal age. This difference was the same in patients with either endometrial carcinoma type I or type II. No association between tumor steroid receptor levels, estradiol concentrations in blood serum, and timing of menopause with intratumoral estradiol contents was discovered. Estradiol concentrations in tumor tissues correlated positively with the clinical stage of disease and rate of tumor invasion (in patients with peripheric/lower type of fat topography), and negatively with tumor differentiation stage (in patients with central/upper type of fat topography) and the percentage of intact double-stranded DNA in normal endometrium. Conclusions: Tumor estrogen content in endometrial cancer has clinical significance that is modified in the presence of certain endocrine characteristics related to insulin resistance. The role of local estrogen production (aromatase activity) in this setting deserves special study.
BackgroundThe article presents the results of a clinical trial on the efficacy and safety of a novel pharmaceutical composition in the form of vaginal suppositories containing diindolylmethane in the course of cervical intraepithelial neoplasia (CIN) I–II conservative treatment. It offers an attractive drug therapy for more personalized prevention of cervical cancer.MethodsA total of 78 women of reproductive age were included. This was a multicenter, randomized, placebo-controlled, double-blind, parallel-group trial with efficacy determined by histological evaluation of cervical biopsies. The efficacy of active drug treatment (100 and 200 mg/day) in both treatment groups was significantly higher in comparison with the placebo group, according to the primary efficacy end point (proportion of patients with complete CIN regression after 90–180 days of the study drug treatment).ResultsThe efficacies were 100.0 % (confidence interval (CI) 95 %: 82.35–100.00 %), 90.5 % (CI 95 %: 69.62–98.83 %), and 61.1 % (CI 95 %: 35.75–82.70 %), for the high dose, low does, and placebo, respectively. Adverse events in the placebo group were reported in 22 % of patients (CI 95 %: 7.5–43.7 %); in the first treatment group (100 mg/day), adverse events were reported in 40.0 % of patients (CI 95 %: 21.1–61.3 %); in the second treatment group (200 mg/day), adverse events were reported in 42.0 % of patients (CI 95 %: 22.1–63.4 %). The differences in side effects between treatment groups treated with the active drug and placebo were statistically significant. No serious adverse events were reported in any of the groups.ConclusionsThus, the use of diindolylmethane in the form of intravaginal suppositories can be effective in patients with CIN I–II and is not accompanied by clinically significant side effects. This approach could be a better option for young women with CIN I–II as it takes in attention their reproductive plans.Trial registrationID: ChiCTR-INR-15007497 (2 December 2015)
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