Levels of the IGF system components in malignant lesions of the lungs with preventive effect of 1,3-diethylbenzimidazolium triiodide in the experiment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15095-e15095
Author(s):  
Lidia K. Trepitaki ◽  
Irina V. Kaplieva ◽  
Elena M. Frantsiyants ◽  
Viktoriya L. Volkova ◽  
Dmitry A. Kharagezov ◽  
...  

e15095 Background: The system of insulin-like growth factors (IGF) is involved in carcinogenesis, since it promotes proliferation and survival of tumor cells. The purpose of the study was an analysis of the dynamics of the IGF system components in the lungs of rats with antitumor effect of 1,3-diethylbenzimidazolium triiodide. Methods: The main group included male (n=27) and female (n=27) white outbred rats with sarcoma 45 inoculated into the subclavian vein (2×106 cells in 0.5 mL saline) but not developed in the lungs due to administration of 1,3-diethylbenzimidazolium triiodide (intragastrically, 0.4 mg/kg once a day according to the regimen: administration for 5 days with a 2-day interval). Control group included males (n=14) and females (n=14) with sarcoma 45 growing in the lungs without treatment. Intact groups included 5 males and 5 females. After 4, 5 and 8 weeks of the experiment animals were decapitated, and levels of IGFI, IGFII, IGFBP1, IGFBP2 and IGFBP3 were measured by ELISA in 10% lung homogenates (CUSABIO BIOTECH Co., Ltd., China). Results: The sarcoma development in the lung was accompanied by the IGFI increase by 2.4-3.0 times in males and by 4.3 times in females, and the opposite IGFII dynamics: an increase in males (by 4.6 times) and decrease in females (by 4.3 times), together with the IGFBP decline. 1,3-diethylbenzimidazolium triiodide upregulated IGFI levels in the lungs of all rats on average by 1.3 times (p<0.05) and normalized IGFII in males, while increasing it in females by 1.6 times (p<0.05), together with higher (compared to controls) IGFBP levels. Conclusions: Preventive antitumor effect of 1.3-diethylbenzimidazolium triiodide is based on the stabilization of the IGF system grossly altered during the malignant process development in the lung.

2020 ◽  
Vol 7 (4) ◽  
pp. 27-35
Author(s):  
E. M. Frantsiyants ◽  
I. V. Kaplieva ◽  
L. K. Trepitaki

Purpose of the study. Analyzing the dynamics of VEGF-А, TGF-β and their receptors in the lung tissues in rats with antitumor effect of 1,3-diethylbenzimidazolium triiodide (Stellanin).Material and methods. The study included white outbred rats weighing 180–220 g. The main group included males (n=27) and females (n=27) with sarcoma 45 (s45) inoculated into the subclavian vein but not developed in the lungs (2×106 cells in 0.5 ml of saline) due to the subsequent intragastric administration of Stellanin (0.4 mg/kg once a day) according to an intermittent scheme: administration for 5 days and a break for 2 days. The control group included males (n=14) and females (n=14) without treatment with growing s45 in the lungs. Intact groups included 5 males and 5 females. After 4, 5 and 8 weeks of the experiment animals were decapitated, and levels of VEGF-A, sVEGF-R1, sVEGF-R2, TGF-β and sTGFβR2 were measured in 10% lung homogenates by ELISA (CUSABIO BIOTECH Co., Ltd., China).Results. Lung tissues of intact females showed 1.4 times (p<0.05) lower VEGF-А and 3.3 times higher sVEGF-R1, compared to males. The development of tumors in all control rats was accompanied by the VEGF-А increase (by 1.6–3.0 times) and the TGF-β reduction (by 3 times). The dynamics of both VEGF receptors differed in males and females. The levels of sVEGF-R1 in males increased by 1.5 times (p<0.05), while in females it decreased by 1.8 times (p<0.05), and as a result, the levels became similar in all animals. The levels of sVEGF-R2 in males decreased by 2 times, and in females it increased by 1.4 times (p<0.05), so the sVEGF-R2 content in females became 2.4 times higher than in males. In two-thirds of rats, Stellanin prevented s45 development in the lungs due to inhibition of VEGF-A growth by more than 2.0 times and an increase in concentrations of sVEGF-R1 by 10.0 times and TGF-β by 6.0 times, together with normalization of sVEGF-R2 and sTGFβR2.Conclusions. Stellanin prevents the development of malignant process in the lungs by inhibiting neoangiogenesis (deficiency of VEGF-A and excess of sVEGF-R1) and suppressing the proliferation of malignant cells (TGF-β growth).


2004 ◽  
Vol 83 (11) ◽  
pp. 832-836 ◽  
Author(s):  
H. Werner ◽  
J. Katz

The insulin-like growth factors (IGF) are a family of growth factors, receptors and binding proteins that are involved in numerous growth and differentiation processes, as well as in various pathological conditions. The aim of this review is to summarize data that has been accumulating in recent years linking the IGF system to a number of physiological and pathological oral processes. The IGF system fulfills an important role in growth and development of teeth, mandible, maxillae, and tongue. It has been postulated that IGF-I may be of great value in the treatment of periodontal defects and in tissue healing. Furthermore, IGF-II has been shown to be overexpressed in salivary gland adenomas, suggesting that aberrant IGF signaling may be a key factor in the etiology of oral malignancies. Understanding the role and regulation of IGF system components in salivary glands and other oral structures will be of significant basic and clinical relevance.


2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Somayeh Pouriamehr ◽  
Haleh Barmaki ◽  
Mozhdeh Rastegary ◽  
Farzaneh Lotfi ◽  
Mohsen Nabi Afjadi

Abstract Objective The insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are thought to play a significant role in metabolic pathways and glucose metabolism. Unregulated levels of IGFs/IGFBPs have been associated with the development of glucose intolerance and metabolic syndrome X (MSx). We hypothesized that change of IGFs/IGFBPs levels could increase the risk of MSx; thus, this study aimed to evaluate the serostatus of IGFs/IGFBPs in individuals with MSx. Results After adjustment for metabolic parameters, MSx patients had a lower level of IGF-1, IGFBP-1, and IGFBP-2 compared with subjects in the control group. Further analysis revealed a positive correlation between serum levels of IGF-1 and IGF-2 (p < 0.05), as well as serum IGFBP-3 and IGF-2 (p < 0.05). Also, the statistical analysis showed a negative association of serum IGF-1 with plasma glucose and total cholesterol levels (p < 0.05). Besides, a negative relationship was found between serum concentrations of IGF-1/IGF-2 and the risk of developing MSx. These data indicated that some components of IGFs/IGFBPs are linked with the pathogenesis of MSx. In conclusion, these inverse associations showed a possible linkage between the IGF/IGFBP signaling pathway and the development of MSx. It seems the decreased concentrations of IGFs edmay be regarded as a potential biomarker for early diagnosis or even prognosis of MSx but need more systematic studies to confirmed it.


2021 ◽  
Vol 74 (8) ◽  
pp. 1925-1930
Author(s):  
Nataliia S. Pidchenko ◽  
Mykola V. Krasnoselskyi ◽  
Nataliia A. Mitriaieva ◽  
Lidiya V. Grebenik ◽  
Olha M. Astapieva ◽  
...  

The aim is to study the level of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-2 (IGF-2) in the blood serum of patients with papillary thyroid cancer, depending on the main clinical and morphological features of the disease. Materials and methods: The material was the information about 60 patients with papillary thyroid cancer (group 1). In group 2 there were 10 patients without oncopathology. All patients underwent clinical examination after total thyroidectomy before special treatment (radioiodine therapy): ultrasound diagnosis of the neck, confirmed diagnosis of papillary thyroid cancer by morphological examination of operative material. All patients underwent anthropometric studies (height, weight), on the basis of which the body mass index (BMI) was calculated. The study program also included determination of the level of thyroid-stimulating hormone of the pituitary gland (TSH), thyroglobulin (TG), antibodies to thyroglobulin (AB-TG). It was also determined the serum glucose level. In order to assess insulin resistance, the HOMA-IR index was calculated. All patients were tested for serum IGF-1 and IGF-2. Results: In the blood serum of patients with papillary thyroid cancer in 63% of patients the level of IGF-1 and in 85% – IGF-2 was probably higher than in the control group. There is a relationship between the level of IGF-1, IGF-2 and elevated level of proliferating factor – insulin in the serum of patients with papillary thyroid cancer. This may indicate an aggressive potential of the disease (i.e. clinical data on the prevalence of papillary thyroid cancer coincide with laboratory data). There was found a relationship between the expression of IGF-1, IGF-2 and insulin: at elevated levels of insulin> 24.9 μIU/ml, IGF-1 increases 4.2 times, and IGF-2 – 2.5 times. Evaluation of the relationship between the level of IGF-1 and IGF-2 and cervical lymph node involvement shows that in the absence of lesion (N0) there is an increase in these indicators by 2.2 and 1.8 times, respectively. Conclusions: The signaling system of insulin-like growth factors (IGF-1 and IGF-2) plays an important role in the occurrence and progression of malignant tumors. It is especially true for papillary thyroid cancer, so its components can be considered as potential diagnostic and prognostic markers of the disease and targets for anticancer therapy.


2005 ◽  
Vol 58 (11-12) ◽  
pp. 558-562 ◽  
Author(s):  
Tatjana Radosavljevic ◽  
Vera Todorovic ◽  
Danijela Vucevic ◽  
Branka Sikic

Introduction Growth is regulated by the interaction of environmental signals with endogenous neuroendocrine responses to the genetic programs that determine the body plan. The insulin-like growth factors (IGFs) are integral components of multiple systems controlling both growth and metabolism. The IGF system The IGF system is thought to be more complex than other endocrine systems, as genes for six IGF-binding proteins (IGFBPs) have been identified so far. The IGFs play a critical role in both cell cycle control and apoptosis, two functions involved in regulation of tumorigenesis. Insulin-like growth factor-I (IGF-I) is essential for normal growth. Confirmation of the significance of IGF-I in human physiology was obtained by the discovery of a patient with intrauterine growth retardation and postnatal growth failure associated with a mutation in the IGF-1 gene. Stages of evolution of the somatomedin hypothesis The original somatomedin hypothesis postulated that somatic growth was regulated by growth hormone's (GH's) stimulation of hepatic IGF-1 production, with IGF-1 acting in an endocrine fashion to promote growth. The dual effectors theory proposed an alternative view, involving direct effects by GH on peripheral tissues not mediated by IGF-1 and GH-stimulated local IGF-1 production for autocrine/paracrine action. It is now clear that G H stimulates the formation of ternary IGF binding complex, which stabilizes IGF-I in the serum.


2019 ◽  
Vol 20 (18) ◽  
pp. 4440 ◽  
Author(s):  
Neirijnck ◽  
Papaioannou ◽  
Nef

Persistent research over the past few decades has clearly established that the insulin-like family of growth factors, which is composed of insulin and insulin-like growth factors 1 (IGF1) and 2 (IGF2), plays essential roles in sexual development and reproduction of both males and females. Within the male and female reproductive organs, ligands of the family act in an autocrine/paracrine manner, in order to guide different aspects of gonadogenesis, sex determination, sex-specific development or reproductive performance. Although our knowledge has greatly improved over the last years, there are still several facets that remain to be deciphered. In this review, we first briefly outline the principles of sexual development and insulin/IGF signaling, and then present our current knowledge, both in rodents and humans, about the involvement of insulin/IGFs in sexual development and reproductive functions. We conclude by highlighting some interesting remarks and delineating certain unanswered questions that need to be addressed in future studies.


2009 ◽  
Vol 28 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Milena Weber ◽  
Ivona Baričević-Jones ◽  
Romana Masnikosa ◽  
Dejan Filimonović ◽  
Željko Miković ◽  
...  

Receptors and Binding Proteins for Insulin and Insulin-Like Growth Factors in the Placenta of Healthy Mothers and Mothers with Insulin-Dependent Diabetes Mellitus The IGF system of human placenta consists of insulin-like growth factors (IGF)-I and -II, their receptors (IGF-1R and IGF-2R), and binding proteins (IGFBP-1 to -6). Due to many structural and metabolic similarities with insulin, the IGF system cannot be examined separately from insulin and its receptor (IR). In this study gel filtration was used to detect solubilized membrane proteins of the placenta obtained from healthy mothers and mothers with IDDM. In order to detect placental membrane proteins that bind IGF molecules (and insulin), the solubilized membranes were incubated with each of the three 125I-labelled ligands: 125I-IGF-I, 125I-IGF-II and 125I-insulin prior to gel filtration chromatography. The biochemical evidence of the presence of receptors for insulin and IGFs, as well as that of IGFBP-1 were obtained by immunoblotting. Herein we demonstrated that, considering IGF and insulin receptor content, the placental tissue obtained from mothers with IDDM was not different from that obtained from healthy mothers. However, the concentration of IGFBP-1 differed between the examined placentas. IDDM in mothers caused an increase in the amount of IGFBP-1 in their placentas and, consequently, the amount of the labelled ligand bound to it. The redistribution of IGFs between the receptors and IGFBP-1 may be involved in regulatory mechanisms in the placenta of mothers with IDDM.


2007 ◽  
Vol 26 (1) ◽  
pp. 17-24
Author(s):  
Olgica Nedić ◽  
Judith Nikolić ◽  
Vesna Malenković ◽  
Ivona Baričević-Jones

Insulin-Like Growth Factors (Igfs) And Their Binding Proteins (Igfbps) As Biomarkers of Catabolism The life of an organism depends on its capacity to maintain equilibrium. Disease induces acute adaptive responses specific to the stimulus and the organism achieves stability through change. These changes are associated with increased growth hormone resistance and activity of the hypothalamic-pituitary-adrenal axis, altered insulin response and cytokine synthesis and, closely related to all these events, alteration of the complex system interrelating insulin-like growth factors (IGFs), IGF-binding proteins (IGFBPs) and their receptors. This review aims to provide an overview of the results obtained in our laboratory from studies of the IGF system in patients with metabolic disturbances caused by infection, hepatobiliary and gastrointestinal diseases, open or laparoscopic surgery and postoperative sepsis.


2021 ◽  
Vol 70 (3) ◽  
pp. 65-74
Author(s):  
Margarita S. Florova ◽  
Maria I. Yarmolinskaya ◽  
Natalya N. Tkachenko ◽  
Gulrukhsor Kh. Tolibova ◽  
Tatyana G. Tral

BACKGROUND: Growth factors play an important role in the pathogenesis of genital endometriosis. Insulin and insulin-like growth factors are involved in mitosis and differentiation in the endometrium during the menstrual cycle and early pregnancy, and are likely to indirectly affect the invasion of the endometrium during retrograde menstruation and the development of pain syndrome in endometriosis. However, the available literature data on insulin-like growth factors and insulin in the endometrium and endometrioid heterotopies in patients with genital endometriosis are scarse and contradictory. AIM: The aim of this study was to investigate the expression of insulin receptors and insulin-like growth factor I receptors in the eutopic endometrium and endometrioid heterotopies of patients with genital endometriosis. MATERIALS AND METHODS: This cross-sectional study included immunohistochemical analysis of surgical material obtained from two groups of women in the proliferative phase of the menstrual cycle: patients with endometriosis who received surgical treatment (endometrium and endometrioid heterotopies) and patients without endometriosis who were examined due to infertility (endometrium). The study also included investigation of carbohydrate metabolism (glucose tolerance test) and determination of blood serum insulin-like growth factor I, insulin and sex hormone levels. The material was stained to detect the expression of insulin receptors and insulin-like growth factor I receptors. Then, the relative area and optical density of the receptor expression were determined and the obtained data were analyzed statistically. RESULTS: We analyzed the examination results of 131 women matched in age and weight and height characteristics: 101 patients with genital endometriosis and 30 patients in the control group. Carbohydrate metabolism was characterized by a 2.1-fold increase in glucose-stimulated insulin secretion in patients with genital endometriosis compared with the control subjects. The blood level of insulin-like growth factor I did not differ in the study groups. Statistically significant differences in receptor expression were obtained between the groups. In the endometrium of patients with genital endometriosis, the optical density of insulin receptors was lower (p = 0.007) and the expression of insulin-like growth factor I receptors higher (p = 0.002) compared to the endometrium of the control subjects. The median values of insulin receptor expression in endometrioid heterotopies were decreased compared to the endometrium of the control group (p 0.001). The expression of insulin-like growth factor I receptors in endometrioid heterotopies was reduced compared to the endometrium of the same patients (p 0.001). CONCLUSIONS: The data obtained indicate significant features in the functioning of the insulin / insulin-like growth factor I system in patients with genital endometriosis: glucose-stimulated insulin secretion and relative endometrial insulin resistance due to the decreased expression of insulin receptors and the increased expression of insulin-like growth factor I receptors in the endometrium.


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