scholarly journals Growth hormone, somatomedins and cancer risk

2020 ◽  
Vol 2 (2) ◽  
pp. 23-30
Author(s):  
Jarosław Kozakowski ◽  
Piotr Dudek ◽  
Wojciech Zgliczyński
Keyword(s):  
Growth Hormone ◽  
Growth Factors ◽  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Signal Transmission ◽  
Epidemiological Studies ◽  
Healthy Elderly ◽  
Reduce Life Expectancy ◽  
Common Opinion ◽  
Dependent Growth

Growth hormone (GH) promotes growth and development in children and is the meaningful co-regulator of the metabolism in adulthood. GH may act directly, through its receptor (GHR), as well as via mediators – insulin-like growth factors: IGF-1, i.e. somatomedin C and IGF-2. Moreover, GH and two growth factors are involved in the mechanisms of cell proliferation, differentiation and survival, hence their oncogenic potential is propounded. Indeed, GH, somatomedins and their receptors are found abundantly in normal and cancer cells in several tissues. It has been shown in animal and human trials that polymorphisms and mutations that increase signal transmission from the GH and IGF-1 receptor are associated with more frequent tumors development and reduce life expectancy. Numerous epidemiological studies have confirmed a clear relationship between GH/IGF-1 level in circulation and a cancer-dependent morbidity and mortality. It dictates caution in case of treatment with use of growth hormone. Such replacement therapy is recommended in cases of GH deficiency. In the common opinion of scientific societies such treatment is generally safe, although in some cases unambiguous opinion in this field cannot be determined yet. On the other hand, on the basis of available evidence, GH cannot be recommended for use by the healthy elderly (ani-aging medicine), bearing in mind that GH decline with age may represent a beneficial adaptation to ageing. Understanding the molecular mechanisms by which GH and GH-dependent growth factors affect cell metabolism and proliferation will allow to use them in oncology in the future.

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.

Oxygen-sensitive regulation and neuroprotective effects of growth hormone-dependent growth factors during early postnatal development

2017 ◽  
Vol 312 (4) ◽  
pp. R539-R548 ◽  
Author(s):  
Susan Jung ◽  
Gudrun Boie ◽  
Helmuth-Guenther Doerr ◽  
Regina Trollmann
Keyword(s):  
Growth Hormone ◽  
Growth Factors ◽  
Postnatal Development ◽  
Energy Homeostasis ◽  
Apoptotic Cell ◽  
Mrna Levels ◽  
Neuroprotective Effects ◽  
Early Postnatal Development ◽  
Reduced Body ◽  
Dependent Growth

Perinatal hypoxia severely disrupts metabolic and somatotrophic development, as well as cerebral maturational programs. Hypoxia-inducible transcription factors (HIFs) represent the most important endogenous adaptive mechanisms to hypoxia, activating a broad spectrum of growth factors that contribute to cell survival and energy homeostasis. To analyze effects of systemic hypoxia and growth hormone (GH) therapy (rhGH) on HIF-dependent growth factors during early postnatal development, we compared protein (using ELISA) and mRNA (using quantitative RT PCR) levels of growth factors in plasma and brain between normoxic and hypoxic mice (8% O2, 6 h; postnatal day 7, P7) at P14. Exposure to hypoxia led to reduced body weight ( P < 0.001) and length ( P < 0.04) compared with controls and was associated with significantly reduced plasma levels of mouse GH ( P < 0.01) and IGF-1 ( P < 0.01). RhGH abrogated these hypoxia-induced changes of the GH/IGF-1 axis associated with normalization of weight and length gain until P14 compared with controls. In addition, rhGH treatment increased cerebral IGF-1, IGF-2, IGFBP-2, and erythropoietin mRNA levels, resulting in significantly reduced apoptotic cell death in the hypoxic, developing mouse brain. These data indicate that rhGH may functionally restore hypoxia-induced systemic dysregulation of the GH/IGF-1 axis and induce upregulation of neuroprotective, HIF-dependent growth factors in the hypoxic developing brain.

scholarly journals Biophysical characterization of melanoma cell phenotype markers during metastatic progression

2021 ◽  
Author(s):  
Anna Sobiepanek ◽  
Alessio Paone ◽  
Francesca Cutruzzolà ◽  
Tomasz Kobiela
Keyword(s):  
Molecular Mechanisms ◽  
Cell Metabolism ◽  
Structural Features ◽  
Protein Glycosylation ◽  
Cell Phenotype ◽  
Metastatic Progression ◽  
Label Free ◽  
Serine Threonine Kinase ◽  
Biophysical Characterization ◽  
Viscoelastic Parameters

AbstractMelanoma is the most fatal form of skin cancer, with increasing prevalence worldwide. The most common melanoma genetic driver is mutation of the proto-oncogene serine/threonine kinase BRAF; thus, the inhibition of its MAP kinase pathway by specific inhibitors is a commonly applied therapy. However, many patients are resistant, or develop resistance to this type of monotherapy, and therefore combined therapies which target other signaling pathways through various molecular mechanisms are required. A possible strategy may involve targeting cellular energy metabolism, which has been recognized as crucial for cancer development and progression and which connects through glycolysis to cell surface glycan biosynthetic pathways. Protein glycosylation is a hallmark of more than 50% of the human proteome and it has been recognized that altered glycosylation occurs during the metastatic progression of melanoma cells which, in turn facilitates their migration. This review provides a description of recent advances in the search for factors able to remodel cell metabolism between glycolysis and oxidative phosphorylation, and of changes in specific markers and in the biophysical properties of cells during melanoma development from a nevus to metastasis. This development is accompanied by changes in the expression of surface glycans, with corresponding changes in ligand-receptor affinity, giving rise to structural features and viscoelastic parameters particularly well suited to study by label-free biophysical methods.

scholarly journals The Effect of Alcohol on Telomere Length: A Systematic Review of Epidemiological Evidence and a Pilot Study during Pregnancy

2021 ◽  
Vol 18 (9) ◽  
pp. 5038
Author(s):  
Andrea Maugeri ◽  
Martina Barchitta ◽  
Roberta Magnano San Lio ◽  
Maria Clara La Rosa ◽  
Claudia La Mastra ◽  
...  
Keyword(s):  
Systematic Review ◽  
Pilot Study ◽  
Alcohol Consumption ◽  
Telomere Length ◽  
Molecular Mechanisms ◽  
Epidemiological Studies ◽  
Potential Association ◽  
Significant Difference ◽  
Periconceptional Period ◽  
Using Data

Several studies—albeit with still inconclusive and limited findings—began to focus on the effect of drinking alcohol on telomere length (TL). Here, we present results from a systematic review of these epidemiological studies to investigate the potential association between alcohol consumption, alcohol-related disorders, and TL. The analysis of fourteen studies—selected from PubMed, Medline, and Web of Science databases—showed that people with alcohol-related disorders exhibited shorter TL, but also that alcohol consumption per se did not appear to affect TL in the absence of alcohol abuse or dependence. Our work also revealed a lack of studies in the periconceptional period, raising the need for evaluating this potential relationship during pregnancy. To fill this gap, we conducted a pilot study using data and samples form the Mamma & Bambino cohort. We compared five non-smoking but drinking women with ten non-smoking and non-drinking women, matched for maternal age, gestational age at recruitment, pregestational body mass index, and fetal sex. Interestingly, we detected a significant difference when analyzing relative TL of leukocyte DNA of cord blood samples from newborns. In particular, newborns from drinking women exhibited shorter relative TL than those born from non-drinking women (p = 0.024). Although these findings appeared promising, further research should be encouraged to test any dose–response relationship, to adjust for the effect of other exposures, and to understand the molecular mechanisms involved.

scholarly journals Neurotrophins as Key Regulators of Cell Metabolism: Implications for Cholesterol Homeostasis

2021 ◽  
Vol 22 (11) ◽  
pp. 5692
Author(s):  
Mayra Colardo ◽  
Noemi Martella ◽  
Daniele Pensabene ◽  
Silvia Siteni ◽  
Sabrina Di Bartolomeo ◽  
...  
Keyword(s):  
Growth Factors ◽  
Cholesterol Metabolism ◽  
System Development ◽  
Cell Metabolism ◽  
Redox Balance ◽  
Nervous System Development ◽  
Cholesterol Homeostasis ◽  
Signaling Cascades ◽  
Target Cells ◽  
The Impact

Neurotrophins constitute a family of growth factors initially characterized as predominant mediators of nervous system development, neuronal survival, regeneration and plasticity. Their biological activity is promoted by the binding of two different types of receptors, leading to the generation of multiple and variegated signaling cascades in the target cells. Increasing evidence indicates that neurotrophins are also emerging as crucial regulators of metabolic processes in both neuronal and non-neuronal cells. In this context, it has been reported that neurotrophins affect redox balance, autophagy, glucose homeostasis and energy expenditure. Additionally, the trophic support provided by these secreted factors may involve the regulation of cholesterol metabolism. In this review, we examine the neurotrophins’ signaling pathways and their effects on metabolism by critically discussing the most up-to-date information. In particular, we gather experimental evidence demonstrating the impact of these growth factors on cholesterol metabolism.

Angiogenesis: molecular mechanisms and functional interactions

2003 ◽  
Vol 89 (01) ◽  
pp. 190-197 ◽  
Author(s):  
Georg Breier ◽  
Hellmut Augustin
Keyword(s):  
Growth Factors ◽  
Research Program ◽  
Tumor Invasion ◽  
Molecular Mechanisms ◽  
Precursor Cells ◽  
Invasion And Metastasis ◽  
Angiogenic Growth Factors ◽  
Cell Contacts ◽  
Functional Interactions ◽  
Biannual Meeting

SummaryThe German Priority Research Program “Angiogenesis” (www.angiogenese.de) hosts a biannual meeting in the Kloster Seeon in Southern Germany. The 2nd Kloster Seeon Meeting “Angiogenesis: Molecular Mechanisms and Functional Interactions” was held in September 2002. It included sessions on hypoxia, the biology of endothelial precursor cells, angiogenic growth factors including VEGFs, the angiopoietins, ephrins, and FGFs, mechanisms of vascular sprouting and cell-cell contacts during angiogenesis, angiogenic signaling, lymphangiogenesis, angiogenesis during tumor invasion and metastasis, and on novel angiomanipulatory therapies. This report summarizes the key findings reported during the platform presentations of the meeting.

scholarly journals High-Risk Human Papillomavirus and Tobacco Smoke Interactions in Epithelial Carcinogenesis

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2201 ◽  
Author(s):  
Francisco Aguayo ◽  
Juan P. Muñoz ◽  
Francisco Perez-Dominguez ◽  
Diego Carrillo-Beltrán ◽  
Carolina Oliva ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
High Risk ◽  
Tobacco Smoke ◽  
Molecular Mechanisms ◽  
Complex Mixture ◽  
Epidemiological Studies ◽  
Hpv Infection ◽  
Oncogenic Viruses ◽  
Cancer Initiation ◽  
Physical Environmental Factors

Cervical, anogenital, and some head and neck cancers (HNC) are etiologically associated with high-risk human papillomavirus (HR-HPV) infection, even though additional cofactors are necessary. Epidemiological studies have established that tobacco smoke (TS) is a cofactor for cervical carcinogenesis because women who smoke are more susceptible to cervical cancer when compared to non-smokers. Even though such a relationship has not been established in HPV-related HNC, a group of HPV positive patients with this malignancy are smokers. TS is a complex mixture of more than 4500 chemical compounds and approximately 60 of them show oncogenic properties such as benzo[α]pyrene (BaP) and nitrosamines, among others. Some of these compounds have been evaluated for carcinogenesis through experimental settings in collaboration with HR-HPV. Here, we conducted a comprehensive review of the suggested molecular mechanisms involved in cooperation with both HR-HPV and TS for epithelial carcinogenesis. Furthermore, we propose interaction models in which TS collaborates with HR-HPV to promote epithelial cancer initiation, promotion, and progression. More studies are warranted to clarify interactions between oncogenic viruses and chemical or physical environmental factors for epithelial carcinogenesis.

G-protein-coupled receptors signalling at the cell nucleus: an emerging paradigmThis paper is one of a selection of papers published in this Special Issue, entitled The Nucleus: A Cell Within A Cell.

2006 ◽  
Vol 84 (3-4) ◽  
pp. 287-297 ◽  
Author(s):  
Fernand Gobeil ◽  
Audrey Fortier ◽  
Tang Zhu ◽  
Michela Bossolasco ◽  
Martin Leduc ◽  
...  
Keyword(s):  
G Protein ◽  
Cell Nucleus ◽  
Intracellular Signaling ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Cell Metabolism ◽  
Hormone Secretion ◽  
G Protein Coupled Receptors ◽  
A Cell ◽  
G Protein Coupled

G-protein-coupled receptors (GPCRs) comprise a wide family of monomeric heptahelical glycoproteins that recognize a broad array of extracellular mediators including cationic amines, lipids, peptides, proteins, and sensory agents. Thus far, much attention has been given towards the comprehension of intracellular signaling mechanisms activated by cell membrane GPCRs, which convert extracellular hormonal stimuli into acute, non-genomic (e.g., hormone secretion, muscle contraction, and cell metabolism) and delayed, genomic biological responses (e.g., cell division, proliferation, and apoptosis). However, with respect to the latter response, there is compelling evidence for a novel intracrine mode of genomic regulation by GPCRs that implies either the endocytosis and nuclear translocation of peripheral-liganded GPCR and (or) the activation of nuclearly located GPCR by endogenously produced, nonsecreted ligands. A noteworthy example of the last scenario is given by heptahelical receptors that are activated by bioactive lipoids (e.g., PGE2 and PAF), many of which may be formed from bilayer membranes including those of the nucleus. The experimental evidence for the nuclear localization and signalling of GPCRs will be reviewed. We will also discuss possible molecular mechanisms responsible for the atypical compartmentalization of GPCRs at the cell nucleus, along with their role in gene expression.

scholarly journals When nutrition interacts with osteoblast function: molecular mechanisms of polyphenols

2009 ◽  
Vol 22 (1) ◽  
pp. 68-81 ◽  
Author(s):  
Anna Trzeciakiewicz ◽  
Véronique Habauzit ◽  
Marie-Noëlle Horcajada
Keyword(s):  
Bone Health ◽  
Molecular Mechanisms ◽  
Vegetable Intake ◽  
Cell Metabolism ◽  
Bone Cell ◽  
Mitogen Activated Protein Kinase ◽  
Present Review ◽  
Activator Protein 1 ◽  
Cellular Signalling ◽  
Osteoblast Function

Recent research has provided insights into dietary components that may optimise bone health and stimulate bone formation. Fruit and vegetable intake, as well as grains and other plant-derived food, have been linked to decreased risk of major chronic diseases including osteoporosis. This effect has been partially attributed to the polyphenols found in these foods. Thus, it has been suggested that these compounds may provide desirable bone health benefits through an action on bone cell metabolism. The present review will focus on how some polyphenols can modulate osteoblast function and reports which cellular signalling pathways are potentially implicated. However, to date, despite numerous investigations, few studies have provided clear evidence that phenolic compounds can act on osteoblasts. Polyphenols cited in the present review seem to be able to modulate the expression of transcription factors such as runt-related transcription factor-2 (Runx2) and Osterix, NF-κB and activator protein-1 (AP-1). It appears that polyphenols may act on cellular signalling such as mitogen-activated protein kinase (MAPK), bone morphogenetic protein (BMP), oestrogen receptor and osteoprotegerin/receptor activator of NF-κB ligand (OPG/RANKL) and thus may affect osteoblast functions. However, it is also important to take in account the possible interaction of these compounds on osteoclast metabolism to better understand the positive correlation reported between the consumption of fruit and vegetables and bone mass.

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