THE RELATIONSHIP BETWEEN METABOLIC DISORDERS AND TUMOR PROGRESSION: REVIEW OF PRESENT DATA AND NEW THERAPEUTIC TARGETS

Background. Type 2 diabetes mellitus, obstructive sleep apnea, osteoarthritis and certain types of cancer are known to correlate with obesity. The mechanisms underlying the link between metabolic disorders and cancer remain obscure, yet assuming a potentially important role of reduced insulin sensitivity, altered glucose metabolism in tumor cells (the so-called Warburg effect), changes in the spectrum of secreted adipokines or interaction with their cognitive receptors as well as changes in steroid sex hormone production.Material and methods. A search for articles published in peer-reviewed journals indexed in pubmed, Wos, scopus and Rsci was carried out. More than 150 articles devoted to the study of the relationship between metabolic disorders and tumor progression were analyzed, of which 69 were included in this review.Results. The main strategy of anticancer therapy is to suppress the proliferation of tumor cells and metastasis. However, one should take into consideration a significant role of additional factors that can enhance side effects of anticancer therapy, ensure the resistance of tumor cells to chemotherapy or change cancer cell metabolic profile. New data recently emerging in the literature indicate an important function of proteins such as t-cadherin and urokinase receptor (upar) and their possible involvement in the regulation of tumor cell metabolism, in particular, sensitivity to insulin and adipose tissue hormones. The review encompasses recent data on the involvement of t-cadherin and upar in the regulation of metabolism and proposes a model explaining the relationship between these proteins and metabolic disorders associated with the processes of carcinogenesis and chemoresistance of cancer cells.Conclusion. Understanding of the factors and mechanisms that support obesity and metabolic disorders is relevant both for the development of cancer preventive measures and optimization of therapeutic strategies for combating cancer.

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Iron-Bound Lipocalin-2 from Tumor-Associated Macrophages Drives Breast Cancer Progression Independent of Ferroportin

Metabolites ◽

10.3390/metabo11030180 ◽

2021 ◽

Vol 11 (3) ◽

pp. 180

Author(s):

Christina Mertens ◽

Matthias Schnetz ◽

Claudia Rehwald ◽

Stephan Grein ◽

Eiman Elwakeel ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Progression ◽

Tumor Cells ◽

Cancer Progression ◽

Lung Metastases ◽

Expression Profiles ◽

The Cancer Genome Atlas ◽

Lipocalin 2 ◽

Tumor Associated Macrophages

Macrophages supply iron to the breast tumor microenvironment by enforced secretion of lipocalin-2 (Lcn-2)-bound iron as well as the increased expression of the iron exporter ferroportin (FPN). We aimed at identifying the contribution of each pathway in supplying iron for the growing tumor, thereby fostering tumor progression. Analyzing the expression profiles of Lcn-2 and FPN using the spontaneous polyoma-middle-T oncogene (PyMT) breast cancer model as well as mining publicly available TCGA (The Cancer Genome Atlas) and GEO Series(GSE) datasets from the Gene Expression Omnibus database (GEO), we found no association between tumor parameters and Lcn-2 or FPN. However, stromal/macrophage-expression of Lcn-2 correlated with tumor onset, lung metastases, and recurrence, whereas FPN did not. While the total iron amount in wildtype and Lcn-2−/− PyMT tumors showed no difference, we observed that tumor-associated macrophages from Lcn-2−/− compared to wildtype tumors stored more iron. In contrast, Lcn-2−/− tumor cells accumulated less iron than their wildtype counterparts, translating into a low migratory and proliferative capacity of Lcn-2−/− tumor cells in a 3D tumor spheroid model in vitro. Our data suggest a pivotal role of Lcn-2 in tumor iron-management, affecting tumor growth. This study underscores the role of iron for tumor progression and the need for a better understanding of iron-targeted therapy approaches.

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Tocopherols and Tocotrienols—Bioactive Dietary Compounds; What Is Certain, What Is Doubt?

International Journal of Molecular Sciences ◽

10.3390/ijms22126222 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6222

Author(s):

Kacper Szewczyk ◽

Aleksandra Chojnacka ◽

Magdalena Górnicka

Keyword(s):

Vitamin E ◽

Metabolic Disorders ◽

Tissue Concentration ◽

Biological Properties ◽

Biological Role ◽

Future Research ◽

The Past ◽

The Subject ◽

The Relationship

Tocopherols and tocotrienols are natural compounds of plant origin, available in the nature. They are supplied in various amounts in a diet, mainly from vegetable oils, some oilseeds, and nuts. The main forms in the diet are α- and γ-tocopherol, due to the highest content in food products. Nevertheless, α-tocopherol is the main form of vitamin E with the highest tissue concentration. The α- forms of both tocopherols and tocotrienols are considered as the most metabolically active. Currently, research results indicate also a greater antioxidant potential of tocotrienols than tocopherols. Moreover, the biological role of vitamin E metabolites have received increasing interest. The aim of this review is to update the knowledge of tocopherol and tocotrienol bioactivity, with a particular focus on their bioavailability, distribution, and metabolism determinants in humans. Almost one hundred years after the start of research on α-tocopherol, its biological properties are still under investigation. For several decades, researchers’ interest in the biological importance of other forms of vitamin E has also been growing. Some of the functions, for instance the antioxidant functions of α- and γ-tocopherols, have been confirmed in humans, while others, such as the relationship with metabolic disorders, are still under investigation. Some studies, which analyzed the biological role and mechanisms of tocopherols and tocotrienols over the past few years described new and even unexpected cellular and molecular properties that will be the subject of future research.

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Comorbid conditions at chronic obstructive pulmonary disease: the questions under investigation and discussion

Ukrainian Therapeutical Journal ◽

10.30978/utj2021-2-57 ◽

2021 ◽

Author(s):

O. I. Lemko ◽

M. O. Haysak ◽

D. V. Reshetar

Keyword(s):

Chronic Obstructive Pulmonary Disease ◽

Metabolic Syndrome ◽

Pulmonary Disease ◽

Metabolic Disorders ◽

Chronic Obstructive ◽

Comorbid Conditions ◽

Obstructive Pulmonary Disease ◽

The Metabolic Syndrome ◽

Obstructive Sleep

The second part of the review examines in detail the questions of diagnostics and peculiarities of the metabolic syndrome manifestations, which presents the link between most comorbid conditions at patients with chronic obstructive pulmonary disease. The metabolic syndrome is based on the insulin resistance and compensatory hyperinsulinemia, caused by both chronic low‑intensity inflammation and increased adipose tissue, often against the background of aggravated heredity at diabetes mellitus. The authors elucidate aspects of the effects of obesity, cachexia and some endocrine disorders on the disease course. The deficiency of researches on endocrine status, especially thyroid function and related metabolic disorders was emphasized. Possible pathogenetic mechanisms of osteoporosis development in this contingent of patients are considered. The need for further research of the pathogenetic role of vitamin D is discussed. Data on the role of the functional state of kidneys in the development of metabolic disorders in an organism have been presented, though kidney pathology in patients with chronic obstructive pulmonary disease is not currently considered as a comorbid condition. The contradictory literature data on the development of anemia in these patients were analysed. The authors presented data on the development of oncological processes as a systemic manifestation at COPD and performed analysis of common and mutually aggravating mechanisms of the development of these pathological conditions. Attention has been paid to the relationship between gastroesophageal reflux disease, bronchiectasis and obstructive sleep apnea with chronic obstructive pulmonary disease. The prospects of modern genetic research in chronic obstructive pulmonary disease and comorbid conditions have been determined.

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Role of Metabolic Reprogramming in Epithelial–Mesenchymal Transition (EMT)

International Journal of Molecular Sciences ◽

10.3390/ijms20082042 ◽

2019 ◽

Vol 20 (8) ◽

pp. 2042 ◽

Cited By ~ 17

Author(s):

Hyunkoo Kang ◽

Hyunwoo Kim ◽

Sungmin Lee ◽

HyeSook Youn ◽

BuHyun Youn

Keyword(s):

Tumor Progression ◽

Tumor Cells ◽

Molecular Mechanisms ◽

Cancer Metastasis ◽

Epithelial Mesenchymal Transition ◽

Metabolic Reprogramming ◽

Metabolic Enzyme ◽

Diverse Range ◽

Mesenchymal Transition ◽

Altered Glucose

Activation of epithelial–mesenchymal transition (EMT) is thought to be an essential step for cancer metastasis. Tumor cells undergo EMT in response to a diverse range of extra- and intracellular stimulants. Recently, it was reported that metabolic shifts control EMT progression and induce tumor aggressiveness. In this review, we summarize the involvement of altered glucose, lipid, and amino acid metabolic enzyme expression and the underlying molecular mechanisms in EMT induction in tumor cells. Moreover, we propose that metabolic regulation through gene-specific or pharmacological inhibition may suppress EMT and this treatment strategy may be applied to prevent tumor progression and improve anti-tumor therapeutic efficacy. This review presents evidence for the importance of metabolic changes in tumor progression and emphasizes the need for further studies to better understand tumor metabolism.

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Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors

The International Journal of Biological Markers ◽

10.1177/1724600820906155 ◽

2020 ◽

Vol 35 (1_suppl) ◽

pp. 8-11 ◽

Cited By ~ 3

Author(s):

Paola Nisticò ◽

Gennaro Ciliberto

Keyword(s):

Tumor Microenvironment ◽

Tumor Cells ◽

Cancer Progression ◽

Cancer Biology ◽

Tumor Development ◽

Short Paper ◽

Great Relevance ◽

Cellular Components ◽

The Relationship

Our view of cancer biology radically shifted from a “cancer-cell-centric” vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.

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Role of Interleukin-6 and Interleukin-8 Cytokines as Early Diagnostic Markers of Sepsis

Bangladesh Journal of Infectious Diseases ◽

10.3329/bjid.v6i2.46102 ◽

2020 ◽

Vol 6 (2) ◽

pp. 34-38

Author(s):

Mohammad Moniruzzaman ◽

Ashesh Kumar Chowdhury ◽

ASM Areef Ahsan ◽

Md Zakiur Rahman ◽

Saimun Nahar Rumana ◽

...

Keyword(s):

Metabolic Disorders ◽

Serum Levels ◽

Clinicopathological Parameters ◽

Enzyme Linked Immunosorbent Assay ◽

Significant Difference ◽

Relationship Of ◽

The Relationship ◽

Culture Positive ◽

Control Study

Background: Rapid diagnosis is essential for effective therapy among the patients with sepsis. Objectives: The purpose of the present study was to determine the relationship of serum levels of IL-6, IL-8 in patients with various stages of sepsis. Methodology: This case control study was conducted in the Department of Immunology at Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM), Dhaka from January 2015 to December 2015 for a period of one (01) year. All patients had been selected from the ICU of BIRDEM General Hospital with known clinicopathological parameters of sepsis. Serum levels of IL-6 and IL-8 were assessed using Enzyme Linked Immunosorbent Assay (ELISA) method. Results: In this study, a total of 80 subjects was enrolled of which 60 patients were with at least 2 SIRS criteria and 20 healthy age matched controls without SIRS. Significant difference was found in IL-6 and IL-8 values in the patients with bacteriological culture positive and negative group (p<0.05). AUC for IL-6 was 0.710 (95% CI 0.580-0.840), sensitivity 54.16%, specificity 59.09%, PPV 74.28% and NPV 52% with cutoff value >177pg/ml. Conclusion: Elevated levels of serum IL-6 and IL-8 is found in the patients with sepsis Bangladesh Journal of Infectious Diseases 2019;6(2):34-38

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Tumor Immune Microenvironment and Its Related miRNAs in Tumor Progression

Frontiers in Immunology ◽

10.3389/fimmu.2021.624725 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yingying Xing ◽

Guojing Ruan ◽

Haiwei Ni ◽

Hai Qin ◽

Simiao Chen ◽

...

Keyword(s):

T Cells ◽

Tumor Progression ◽

Tumor Cells ◽

Immune Cells ◽

Suppressor Cells ◽

Immune Microenvironment ◽

Non Coding Rna ◽

Tumor Immune Microenvironment ◽

Downstream Gene Expression

MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can participate in the biological processes of tumor, including proliferation, invasion and escape, and exhibit tumor enhancement or inhibition. The tumor immune microenvironment contains numerous immune cells. These cells include lymphocytes with tumor suppressor effects such as CD8+ T cells and natural killer cells, as well as some tumor-promoting cells with immunosuppressive functions, such as regulatory T cells and myeloid-derived suppressor cells. MiRNA can affect the tumor immune microenvironment by regulating the function of immune cells, which in turn modulates the progression of tumor cells. Investigating the role of miRNA in regulating the tumor immune microenvironment will help elucidate the specific mechanisms of interaction between immune cells and tumor cells, and may facilitate the use of miRNA as a predictor of immune disorders in tumor progression. This review summarizes the multifarious roles of miRNA in tumor progression through regulation of the tumor immune microenvironment, and provides guidance for the development of miRNA drugs to treat tumors and for the use of miRNA as an auxiliary means in tumor immunotherapy.

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Activation of the NF-κB Signaling Pathway Promotes Malignancy in Bladder Cancer Cells in a Positive Feedback Manner

10.21203/rs.3.rs-60078/v1 ◽

2020 ◽

Author(s):

Zhenfeng guan ◽

Yi Sun ◽

YaZhuo Jiang ◽

Xinyang Wang ◽

Jinhai Fan

Keyword(s):

Bladder Cancer ◽

Endothelial Cells ◽

Tumor Cell ◽

Tumor Progression ◽

Signaling Pathway ◽

Tumor Cells ◽

Positive Feedback ◽

Umbilical Vein

Abstract Background: The main issue arising from bladder cancer (BCa) is the high relapse ratio and tumor progression, the mechanism of which remains to be elucidated. Interaction of tumor cells with the stroma of microenvironment promoting tumor progression warrants much attention from researchers. Among all stromal cells, endothelial cells (ECs) are exceptional. Numerous studies have investigated its role of angiogenesis, but have not studied immunocyte recruitment and chemokine secretion, the important significance of which in tumor progression has been proven. Meanwhile, to the best of our knowledge, few studies have focused on the direct interaction between tumor cells and ECs in BCa tissue, which was the aim of the present study. Methods: In the present study, immunohistochemical staining is used for detecting the distribution of ECs in BCa tissue, and we use SPSS 19 to analysis the relationship between ECs distribution and tumor grade/stage; inadition, co-curlturing of tumor cell with ECs is usd to mimicking the interaction of tumor cell with ECs, followed by Chamber Assay, BrdU incorporoartion, WB, Qt-PCR, ect, to investiatin the mechanism. Results: The distribution of ECs in BCa tissue is significantly increased according to BCa grade and negatively associated to the time from BCa diagnosis to progression, manifesting as an independent risk factor for BCa prognosis. The following in vitro experiment indicates that the conditional medium from co-culture of tumor cells (T24/J82) with ECs (human umbilical vein endothelial cells, which were used as ECs in the in vitro experiment) contributes to the activation of the NF-ĸB signaling pathway in tumor cells, leading to the upregulation of CXCL1/8. This further results in enhanced tumor cell malignancy and EC recruitment, manifested as a positive feedback loop. Conclusions: The present study provided a further understanding on the role of ECs in BCa progression—not only by angiogenesis but also by interacting with tumor cell dirctly.

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THE ROLE OF ENDORPHIN HORMONES AS PREDICTORS OF PREGNANCY ANXIETY

International Journal of Nursing and Health Services (IJNHS) ◽

10.35654/ijnhs.v2i3.107 ◽

2019 ◽

Vol 2 (3) ◽

pp. 16-21

Author(s):

Putriatri Krimasusini Senudin ◽

Saidah Syamsuddin ◽

Andi Armyn Nurdin

Keyword(s):

Rating Scale ◽

Hormone Production ◽

Cross Sectional ◽

Hormone Levels ◽

Pregnancy Anxiety ◽

Hamilton Anxiety Rating Scale ◽

Keywords Anxiety ◽

Relationship Of ◽

The Relationship

Pregnancy anxiety is a common problem with a prevalence of 14-54% and is the highest in the third trimester. Pregnancy anxiety is associated with neurotransmitter dysregulation and endocrine changes in the Hypothalamus Pituitary Adrenal (HPA) axis pathway through the increase of synthesis and the release of corticotropin-releasing hormone (CRH), Adrenocorticotropic Hormone (ACTH) and cortisol to suppress endorphin hormone production. This study aims to determine the relationship of endorphin hormone levels to pregnancy anxiety. This study was an observational study using a cross-sectional approach to 57 pregnant women. The anxiety level was measured by using the Hamilton Anxiety Rating Scale (HARS) and the ELISA kit with plasma specimens was employed to examine the endorphin hormone levels. The results showed that endorphin hormone levels acted as predictors of pregnancy anxiety (p = 0,000). Keywords: Anxiety, Pregnancy, Endorphin

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THE ROLE OF ASSESSMENT AND CORRECTION OF NUTRITIONAL STATUS IN A COMPREHENSIVE APPROACH TO COVID-19 PATIENT WITH METABOLIC DISORDERS: Review

Inter Collegas ◽

10.35339/ic.8.3.152-156 ◽

2021 ◽

Vol 8 (3) ◽

pp. 152-156

Author(s):

S.V. Ivanchenko ◽

O.M. Kovalyova ◽

A.B. Andrusha

Keyword(s):

Nutritional Status ◽

Inpatient Treatment ◽

Metabolic Disorders ◽

Clinical Course ◽

Respiratory Infections ◽

The Body ◽

Analytical Review ◽

Human Immune ◽

The Relationship

The article is devoted to the problem of coronavirus disease COVID-19 with emphasis on the nutritional status of patients. An analytical review of recent publications related to aspects of nutritional support for people in outpatient and inpatient treatment for COVID-19 is presented. The article highlights the pathogenetic justification of the relationship between the immune response and metabolic balance of the body, the optimal content of trace elements, vitamins, components of lipid metabolism. The importance of nutrition as a strategy to support human immune function is considered. Methods for determining the adequate energy balance of patients with severe COVID-19 are presented. Groups of foods and key nutrients that may affect the consequences and clinical course of respiratory infections are described. The importance of assessing and optimizing nutritional status to improve the clinical course and consequences of COVID-19 in patients with comorbid pre-existing non-communicable diseases, such as diabetes, cardiovascular disease, obesity with systemic inflammation, is emphasized.

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