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16
наука и здравоохранение, №4, 2014
Тезисы
CANCER MORBIDITY IN PATIENTS WITH DIABETES MELLITUS
S. Iskakova1 , O. Urazayev1, E. Bekmukhambetov1, G. Dworacki2
West-Kazakhstan Marat Ospanov State Medical University, Aktobe, Kazakhstan; 2 Poznan University of Medical Science, Poznan, Poland
Despite the progress in health care, the incidence of malignant neoplasms (MN) continues to increase. According to WHO (2013) annually in all over the world primary cancers are detected in 9 million people and cause death of about 5 million people a year. Every day in Kazakhstan more than 80 people develop cancer, and the increase in the number of patients with malignant neoplasms is 5% a year. The explanation for such high morbidity is the presence of numerous predisposing factors, such as unhealthy diet, smoking, increased number of older persons, unfavorable environment, occupational diseases, stress, and concomitant diseases.
According to recent studies, diabetes, every day becoming an epidemic, is highlighted as cancer risk factor for pancreatic cancer, hepatoduodenal cancer, colorectal cancer, breast cancer, bladder and lymphomas (Shikata K, et al., 2013). This increased risk is expressed by statistics as follows: 50% is pancreatic cancer, 30% - of the colon cancer, and 20% - Breast cancer (Larsson et al., 2008).
Currently, the mechanism of effect of diabetes on the development of malignancies is not fully understood. How-
ever, the possible factors and mechanisms of malignancies induction are obesity, hyperglycemia, hyperinsulinemia and insulin-like growth factor-1. Moreover, the treatment of diabetes may alsoinfluence the development for MN. Recently, insulin and insulin analogues significance for malignancies development has been widely discussed. In respect to their potency to stimulate cells proliferation (Pollak et al., 2012). In recent years, first-line antidiabetic agent - metformin was confirmed as inducing anticancer effects. In the observational study of patients receiving metformin (Libby et al. 2009) it was a lower risk of MN development, in comparison to another type 2 diabetic un-treated with metformin. This beneficial effect of metformin was related to the decrease in glycaemia, hyperinsulinemia and increased insulin sensitivity.
Conclusion: well documented high risk of malignant neoplasms development in diabetic patients is the reason for further study focused on diabetes-related mechanisms of normal cells and the effect of antidiabetic therapy on these processes, to increase the effectiveness of treatment and prevention of both pathologies.
ASSOCIATION BETWEEN 53BP1 EXPRESSION AND GENOMIC INSTABILITY IN ONCOCYTIC FOLLICULAR ADENOMA OF THE THYROID
Zhanna Mussazhanova1, Kazuko Shichijo2, Shiro Miura2, Katsuya Matsuda2, Ryota Otsubo2, Masahiro Oikawa3, Kohichiro Yoshiura4, Norisato Mitsutake4, Tatiana Rougounovitch4, Vladimir Saenko4, Hisayoshi Kondo5, Masahiro Ito3, Masahiro Nakashima2*
1Research center, Semey State Medical University, Semey, Kazakhstan;
2Department of Tumor and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
3Department of Pathology, National Hospital Organization Nagasaki Medical Center, Omura, Japan
4Department of Radiation Medical Sciences, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan
5Biostatics Section, Division of Scientific Data Registry, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
We have reported a usefulness of immunofluorescence (IF) analysis for the type of 53BP1 expression, which belongs to DNA damage response (DDR) molecules, to estimate the genomic instability (GIN) in diverse tumorigenesis including thyroid. The expression of 53BP1 nuclear foci (NF) has been found to reflect DNA double strand break caused by various stresses. Accumulation of genetic mutations can induce GIN causing both initiation and progression of cancers. Oncocytic follicular adenomas of the thyroid (OFAs) are neoplasms of follicular cell origin predominantly composed of large and polygonal cells with an eo-sinophilic and granular cytoplasm that is rich in mitochondria. To clarify the GIN of OFA, we analyzed the type of 53BP1 expression in OFA as compared with conventional FA (CFA) by IF and its association between the level of
DNA copy number aberration (CNA) by array-based comparative genomic hybridization (aCGH) as an indicator of GIN. In results, this study demonstrated the ab-normnal/DDR type of 53BP1 expression in OFA and its association with a higher incidence of CNA by aCGH, suggesting a higher level of GIN in OFA than cFa. The mito-chondrial dysfunction may block the apoptotic process resulting in increasing the survival of genetically injured cells and, simultaneously, GIN during tumorigenesis. Furthermore, we observed an amplification of chromosome 1p36 in OFA showing high DDR/abnormal type of 53BP1 expression and its significant positive correlation with the level of TP73expression. Because TP73 belongs to p53 protein family, dysregulation of TP73 transcription may play a critical role during tumorigenesis of OFA.
