Abnormalities of apoptosis of the thyroid gland cells from extratumoral microfollicular tissue

Aim: The aim of this study was to evaluate the frequency of existence of thyroid extratumoral normo- and microfollicular tissue in patients with thyroid carcinoma and peculiarities of apoptosis in mentioned tissue. Materials and Methods: Using samples of normo- and microfollicular thyroid tissue it was determined the content of fragmented DNA and intensity of stimulated internucleosomal DNA fragmentation; activities of caspase-3 and cysteine lysosomal cathepsins. Results: It was found that normofollicular tissue is observed more often in patients with nodal euthyroid goiter but microfollicular tissue is more common for patients with carcinoma. Extratumoral microfollicular tissue was found in the thyroid of patients above 50 years old mostly, and more rarely in young ones. The fragmented DNA concentration in microfollicular tissue was lower by a factor of 3.5 and intensity of stimulated internucleosomal DNA fragmentation was also decreased. Activity both of cathepsin B in lisosomes and caspase-3 in lysates of such tissue was also decreased. Conclusions: The decrease of intensity of spontaneous apoptosis and the absence of its modulation/induction following proapoptotic factors in extratumoral microfollicular thyroid tissue may be considered as a respond of the thyroid gland tissue to an existence of carcinoma

Differentiated thyroid carcinomas associated with chronic thyroiditis: biological and clinical properties

Aim: To determine biological and clinical features of papillary and follicular thyroid carcinomas associated or not associated with chronic thyroiditis. Materials and Methods: The study was conducted by retrospective analysis of medical histories of 2,459 patients with thyroid cancer. Tumor size, its category according to the TNM system, multi-focal properties of tumor growth, carcinoma invasiveness, as well as disease stage, rates of relapses and metastasis, and also cumulative survival rates were analyzed. Results: The tumor size in patients with papillary or follicular carcinoma associated with thyroiditis was smaller compared to the patients without thyroiditis. In the first case, the invasion frequency into extrathyroid structure and into the capsule was also lower. Multi-focal growth of both carcinoma types was registered more frequently in the presence of thyroiditis. The frequency of papillary carcinoma metastasis to lateral cervical lymph nodes was lower in the presence of thyroiditis, the frequency being equal for metastasis into lymph nodes of the VI lymph outflow zone in both groups of patients (with and without thyroiditis). In the presence of thyroiditis, the frequency of distant papillary carcinoma metastasis was decreased, no metastases were detected in patients with follicular carcinoma. In the group of patients with papillary carcinoma there was found no relation between the presence of thyroiditis and disease stage, relapse rates, and mortality levels; however, the risk of follicular carcinoma relapse was significantly lower in patients with thyroiditis. Conclusions: The presence of chronic thyroiditis in papillary carcinoma patients showed a certain positive impact on the course of the disease, in particular, primary tumor growth, invasion, and metastasis. Such effect is even more expressed in the patients with follicular thyroid carcinoma. Key Words: papillary and follicular thyroid carcinomas, autoimmune thyroiditis

Association of 5’AMP-activated protein kinase activity with disease duration and HbA1c content in leukocytes in diabetic patients

Background. 5’AMP-activated protein kinase (AMPK) is an enzyme that controls the cell energy ba­lance. With energetic stress in the cell and an increase in the AMP concentration, ATP is replaced by AMP in the exchange centers, resulting in the allosteric activation of AMPK by phosphorylation of 172 threonine within alpha subunit of LKB1 complex in response to changes in cell energy or CAMKKβ, which activates intracellular Ca2+. The purpose was to study the activity of the main energy sensor of cells — AMPK in leukocytes in patients taking insulin preparations, metformin, and other hypoglycemic drugs in association with disease duration and glycated hemoglobin content. Materials and methods. The diabetic patients receiving single-drug or combined therapy with insulin and its analogues, metformin, dapagliflozin and sulfonylureas were randomized into 5 groups: the first group — with an HbA1c level close to the norm — 6.9–7.6 %; the second group — 7.6–9.0 %; the third group — > 9 %; the fourth group > 10 %; the fifth group — > 11 %. To determine the amount of phospho-AMPK (p-Thr172), ELISA kits were used. To get the calibration curve for the AMPK determination, a kidney cell culture HEK293T of the human embryonic kidney was used, which is recommended by manufacturer as a positive control. Results. It was shown that with increase of blood HbA1c, the level of AMPK activity in leukocytes gradually decreased. With increase of blood HbA1c, the level of AMPK activity in leukocytes gradually decreased. The activity of AMPK in leukocytes of patients with HbA1c > 11 % was more than 3.5-fold lower compared to the group with 6.9–7.6 % of HbA1c; AMPK activity in leukocytes in patients with disease duration of 20 years was 3-fold lower. Thus, the AMPK activity in leukocytes may be an indicator of diabetic compensation in diabetic patients. Conclusions. With increase of blood HbA1c, the level of p-AMPK in leukocytes gradually decreased. AMPK activity in leukocytes in diabetes patients with disease duration of 20 years was 3-fold lower than in patients with 10-year experience