Purpose of the study. An analysis of indices of free radical oxidation and respiration of mitochondria of heart cells in a malignant process in presence of diabetes mellitus and chronic neurogenic pain in experimental animals.Materials and methods. The study included outbred female rats (n=32) and С57ВL/6 female mice (n=84). Experimental groups of rats were: intact group 1 (n=8), control group 1 (n=8) with diabetes mellitus (DM), comparison group 1 (n=8) with standard subcutaneous transplantation of Guerin’s carcinoma, main group 1 (n=8) with Guerin’s carcinoma transplanted after 1 week of persistent hyperglycemia. Experimental groups of mice were: intact group 2 (n=21), control group 2 (n=21) with a model of chronic neurogenic pain (CNP), comparison group 2 (n=21) with standard subcutaneous transplantation of melanoma (B16/F10), main group 2 (n=21) (CNP+B16/F10) with melanoma transplanted 3 weeks after the CNP model creation. Heart mitochondria were isolated by differential centrifugation. Levels of cytochrome C (ng/mg of protein), 8-hydroxy-2'-deoxyguanosine (8-OHdG) (ng/mg of protein), and malondialdehyde (MDA) (μmol/g of protein) were measured in mitochondrial samples by ELISA. Statistical analysis was performed using the Statistica 10.0 program.Results. DM in rats upregulated 8-OHdG by 6.3 times and MDA by 1.9 times (р=0.0000) and downregulated cytochrome C by 1.5 times (р=0.0053) in heart cell mitochondria, compared to intact values. DM+Guerin’s carcinoma in rats increased 8-OHdG by 14.0 times and MDA by 1.7 times (р=0.0000) and decreased cytochrome C by 1.5 times (р=0.0000), compared to intact values. CNP in mice did not affect the studied parameters in mitochondria of the heart. CNP+B16/F10 in mice increased 8-OHdG by 7.1 times and MDA by 1.6 times (р=0.0000) and decreased cytochrome C by 1.6 times (р=0.0008).Conclusions. Comorbidity (diabetes mellitus, chronic neurogenic pain) together with malignant pathology aggravates mitochondrial dysfunction of heart cells with destabilization of the respiratory chain mediated by free radical oxidation processes.
To study the effect of comorbid pathology: obesity of degree 2-3 on the level of sex steroid hormones and their receptors in the tumor and its surrounding tissue in patients with endometrial cancer (EC). Materials and methods. In 30 patients with endometrioid adenocarcinoma T1-3N0-1M0 (the main group, 15 females with obesity grade 2-3 (BMI≥35); the reference group 15 females with normal BMI) in samples of the tumor and its perifocal zone taken after surgical treatment, the levels of estradiol (E2), estrone (E1), testosterone (T), progesterone (P4), androgen receptors (AR), progesterone receptors (RP4), estrogen receptors (ERα and ERβ) were determined by ELISA method. Statistical analysis was performed with STATISTICA 10.0. Results. Obese EC patients showed longer healing of postoperative wounds, slow recovery, and more frequent tumor metastasizing to regional lymph nodes. In the tumor samples in all patients, compared with the intact endometrium, the levels of estrogens, testosterone and their receptors were higher. Obesity accompanying the malignant process led to a local increase in the levels of estrogens, testosterone, progesterone and AR, ERα and ERβ in the tumor. In the tumor samples, there were no significant differences from the presence of obesity in the levels of RP4. In the perifocal zone of the tumor in patients with comorbid pathology, compared with the parameters in the reference group, the level of E2, P4 and T was also higher, but the content of all steroid receptors was lower. Conclusion. Obesity aggravates hyperestrogenism and progesterone deficiency in adenocarcinoma and increases its enrichment with the androgen and estrogen receptors with the prevalence of ERα over ERβ that may cause the autocrine-paracrine regulation of the growth and metastasizing of the malignant process in patients with endometrial cancer.
Diabetes mellitus and malignant tumors are among the most common and complex diseases. Epidemiological studies have shown a strong relationship between these pathologies. The causality of this relationship has not yet been unambiguously established, but a number of probable biological mechanisms have been proposed to explain it through the effects of hyperglycemia, hyperinsulinemia on the process of oncogenesis. An important role in this is played by the axis of insulin-like growth factors, their receptors and binding proteins (IGF / IGFR / IGFBP). The review provides data on the structural elements of the insulin / IGF / IGFR / IGFBP signaling axis and their internal relationships in diabetes mellitus and in the development of malignant tumors. Significant changes in the axis that occur during the formation of the diabetic environment prepare the background, which, under certain conditions, can lead to the stimulation or inhibition of tumor development. The considered signaling system, playing a significant role in the physiology of normal cells, often functions as a decisive factor in the survival of tumor cells, providing fine context-dependent regulation of many cellular processes associated with oncogenesis. However, despite many years of in-depth studies of the pathogenesis of diabetes mellitus and malignant tumors, the molecular mechanisms of the relationship between these pathologies are still largely unclear, and the internal heterogeneity of pathologies complicates research and interpretation of the results, leaving many questions.
Purpose of the study. Diabetes mellitus (DM) is considered an independent risk factor for higher cancer incidence and death rates. The system of insulin-like growth factors and their carrier proteins (IGF and IGFBP) and hyperglycemia create favorable conditions for the proliferation and metastasis of cancer cells.Materials and methods. Outbred male and female rats were divided into groups (n = 8 each): controls - with Guerin's carcinoma; main group - Guerin's carcinoma growing in presence of DM. Experimental DM was reproduces in animals by the single intraperitoneal alloxan injection (150 mg/kg body weight). After 10 days of the carcinoma growth, levels of IGF and IGFBP in the tumor and in it's perifocal area were measured using ELISA.Results. DM in females upregulated levels of glucose both in the tumor and in perifocal tissues by 1.8 (p < 0.05) and 8.1 times, respectively, but caused opposite changes in IGF-I - it's increase by 6.3 times in the tumor and decrease by 3.2 times in the perifocal area; as a result, such tumors with small primary nodes were more "aggressive" and actively metastasized. In males, induced DM downregulated levels of glucose, IGF-II and IGFBP2 in the carcinoma by 8.4, 3.1 and 1.7 (p < 0.05) times, respectively, and increased levels of IGF-I and IGFBP2 by 1.4 and 1.3 times (p < 0.05) in the perifocal area without changing glucose levels; as a result, tumor volumes exceeded the values in the standard growth, without metastasizing into visceral organs.Conclusion. We revealed gender differences in changing levels of glucose and IGF both in the tumor and in it's perifocal tissue in rats with Guerin's carcinoma growing in presence of DM; these differences could determine different tumor growth dynamics in male and female rats.
Diabetes mellitus is an additional risk factor for the development of heart diseases, cardiovascular dysfunction and malignant tumors. The aim of the study was to analyze levels of IGF and IGFBP in heart samples of animals with diabetes mellitus and/ or growing Guerin’s carcinoma. The study included white outbred rats of both genders weighing 180-220 g. The rats of each gender were divided into groups of 8 animals: the intact group; test groups 1 (with diabetes) and 2 (with transplanted Guerin’s carcinoma); the main group (transplanted Guerin’s carcinoma growing in the presence of diabetes mellitus). Levels of IGF-I, IGF-II, IGFBP-1, and IGFBP-2 were measured by ELISA (Mediagnost, Germany) in heart homogenates in animals of all groups
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