scholarly journals Diabetes mellitus and cancer: a system of insulin-like growth factors

2021 ◽  
Vol 67 (5) ◽  
pp. 34-42
Author(s):  
E. M. Frantsiyants ◽  
E. I. Surikova ◽  
I. V. Kaplieva ◽  
V. A. Bandovkina ◽  
I. V. Neskubina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factors ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Strong Relationship ◽  
Epidemiological Studies ◽  
Cellular Processes ◽  
Signaling Axis ◽  
Insulin Like Growth Factors

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.

scholarly journals Extended UVB Exposures Alter Tumorigenesis and Treatment Efficacy in a Murine Model of Cutaneous Squamous Cell Carcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Erin M. Burns ◽  
Kathleen L. Tober ◽  
Judith A. Riggenbach ◽  
Donna F. Kusewitt ◽  
Gregory S. Young ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Sun Exposure ◽  
Epidemiological Studies ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Exposure Model ◽  
Uvb Exposure

Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC) development. However, the presumed effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemopreventive.

scholarly journals A Twenty-First Century Cancer Epidemic Caused by Obesity: The Involvement of Insulin, Diabetes, and Insulin-Like Growth Factors

2013 ◽  
Vol 2013 ◽  
pp. 1-37 ◽  
Author(s):  
Rosalyne L. Westley ◽  
Felicity E. B. May
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factors ◽  
Diabetes Mellitus Type 2 ◽  
Diabetes Mellitus Type ◽  
Type I ◽  
Hormone Production ◽  
Type I Igf Receptor ◽  
High Concentrations ◽  
Insulin Like Growth Factors

Obesity has reached epidemic proportions in the developed world. The progression from obesity to diabetes mellitus type 2, via metabolic syndrome, is recognised, and the significant associated increase in the risk of major human cancers acknowledged. We review the molecular basis of the involvement of morbidly high concentrations of endogenous or therapeutic insulin and of insulin-like growth factors in the progression from obesity to diabetes and finally to cancer. Epidemiological and biochemical studies establish the role of insulin and hyperinsulinaemia in cancer risk and progression. Insulin-like growth factors, IGF-1 and IGF-2, secreted by visceral or mammary adipose tissue have significant paracrine and endocrine effects. These effects can be exacerbated by increased steroid hormone production. Structural studies elucidate how each of the three ligands, insulin, IGF-1, and IGF-2, interacts differently with isoforms A and B of the insulin receptor and with type I IGF receptor and explain how these protagonists contribute to diabetes-associated cancer. The above should inform appropriate treatment of cancers that arise in obese individuals and in those with diabetes mellitus type 2. Novel drugs that target the insulin and insulin-like growth factor signal transduction pathways are in clinical trial and should be effective if appropriate biomarker-informed patient stratification is implemented.

scholarly journals Insulin resistance and cancer: the role of insulin and IGFs

2012 ◽  
Vol 20 (1) ◽  
pp. R1-R17 ◽  
Author(s):  
Sefirin Djiogue ◽  
Armel Hervé Nwabo Kamdje ◽  
Lorella Vecchio ◽  
Maulilio John Kipanyula ◽  
Mohammed Farahna ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Cell Proliferation ◽  
Energy Metabolism ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Tumor Development ◽  
Epidemiological Studies ◽  
High Energy

Insulin, IGF1, and IGF2 are the most studied insulin-like peptides (ILPs). These are evolutionary conserved factors well known as key regulators of energy metabolism and growth, with crucial roles in insulin resistance-related metabolic disorders such as obesity, diseases like type 2 diabetes mellitus, as well as associated immune deregulations. A growing body of evidence suggests that insulin and IGF1 receptors mediate their effects on regulating cell proliferation, differentiation, apoptosis, glucose transport, and energy metabolism by signaling downstream through insulin receptor substrate molecules and thus play a pivotal role in cell fate determination. Despite the emerging evidence from epidemiological studies on the possible relationship between insulin resistance and cancer, our understanding on the cellular and molecular mechanisms that might account for this relationship remains incompletely understood. The involvement of IGFs in carcinogenesis is attributed to their role in linking high energy intake, increased cell proliferation, and suppression of apoptosis to cancer risks, which has been proposed as the key mechanism bridging insulin resistance and cancer. The present review summarizes and discusses evidence highlighting recent advances in our understanding on the role of ILPs as the link between insulin resistance and cancer and between immune deregulation and cancer in obesity, as well as those areas where there remains a paucity of data. It is anticipated that issues discussed in this paper will also recover new therapeutic targets that can assist in diagnostic screening and novel approaches to controlling tumor development.

EFFECT OF DIABETES MELLITUS ON THE LEVEL OF GROWTH FACTORS IN GUERIN CARCINOMA IN RATS OF BOTH SEXES

2021 ◽  
pp. 129-140
Author(s):  
E.M. Frantsiyants ◽  
V.A. Bandovkina ◽  
I.V. Kaplieva ◽  
E.I. Surikova ◽  
I.V. Neskubina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Growth Factors ◽  
Malignant Tumors ◽  
Elisa Test ◽  
Main Group ◽  
Female Rats ◽  
Control Group ◽  
Concomitant Disease ◽  
White Rats

Diabetes mellitus is an independent risk factor for a number of malignant diseases. It is associated with increased mortality from cancer. The role of growth factors in the pathophysiology of diabetes mellitus and malignant tumors is dual and not fully defined. The aim of the study was to examine the level of some growth factors and their receptors in the tissue of Guerin carcinoma and its perifocal zone growing in rats of both sexes with diabetes mellitus. Materials and Methods. The authors determined the content of VEGF-A, VEGF-C their receptors sVEGF-R1 and sVEGF-R3, EGF and sEGF-R, TGFβ1 and sTGFβ1-R2, TNFα and sTNFα-R1, FGF21 in the samples of the tumor and the perifocal zone of Guerin carcinoma in nonlinear white rats of both sexes with diabetes mellitus (main group). ELISA test was used for this purpose. The control group consisted of animals with Guerin carcinoma without comorbid pathology. Results. Tumors in female rats (main group) had a higher content of VEGF-C, EGF, TNFα and FGF21, VEGF-C/VEGF-R3, but a lower TGFβ1 level. In the perifocal zone these indicators, except TNFα, were lower than in the control group. In males (main group), TNFα and VEGF-A/VEGF-R1 levels in the tumor were higher. The content of VEGF-C, EGF, EGF-R and TGFβ1 was lower than in the control. At the same time, all the studied parameters were lower in the perifocal zone, except FGF21 and EGF-R. Conclusion. Diabetes mellitus as a concomitant disease decreased the life expectancy of animals of both sexes with Guerin carcinoma. At the same time, high ratios of VEGF-A/VEGF-R1 in males, and VEGF-C/VEGF-R3, EGF/sEGF-R, and FGF21 in females in tumor samples were accompanied by the tumor growth in males and activation of metastatic processes in females. Key words: Guerin carcinoma, diabetes mellitus, rats, growth factors, receptors. Сахарный диабет является самостоятельным фактором риска возникновения ряда злокачественных заболеваний и связан с повышенной смертностью от рака. Роль факторов роста в патофизиологии сахарного диабета и злокачественных опухолей двойственна и до конца не определена. Целью настоящего исследования явилось изучение уровня некоторых факторов роста и их рецепторов в ткани карциномы Герена, растущей на фоне сахарного диабета, и ее перифокальной зоне у крыс обоего пола. Материалы и методы. У нелинейных белых крыс обоего пола в образцах опухоли и перифокальной зоны карциномы Герена, растущей на фоне сахарного диабета (основная группа), методом ИФА определяли содержание VEGF-A, VEGF-C и их рецепторов sVEGF-R1 и sVEGF-R3, EGF и sEGF-R, TGFβ1 и sTGFβ1-R2, TNFα и sTNFα-R1, FGF21. В качестве контрольной группы выступали животные с карциномой Герена без коморбидной патологии. Результаты. У самок крыс основной группы в опухоли было выше содержание VEGF-C, EGF, TNFα и FGF21, VEGF-С/VEGF-R3, но ниже уровень TGFβ1, в перифокальной зоне эти показатели, за исключением TNFα, были ниже, чем в группе контроля. У самцов основной группы в опухоли был выше уровень TNFα и VEGF-A/VEGF-R1, содержание VEGF-C, EGF, EGF-R и TGFβ1 оказалось ниже, чем в контроле. При этом в перифокальной зоне все исследованные показатели были ниже, за исключением FGF21 и EGF-R. Выводы. Сахарный диабет как сопутствующее злокачественному росту заболевание способствовал снижению продолжительности жизни животных обоего пола с карциномой Герена. При этом высокие в образцах опухоли соотношения VEGF-A/VEGF-R1 у самцов, VEGF-С/VEGF-R3, EGF/sEGF-R и FGF21 у самок сопровождались ростом объемов опухоли у самцов и активацией метастатических процессов у самок. Ключевые слова: карцинома Герена, сахарный диабет, крысы, факторы роста, рецепторы.

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