scholarly journals On the Role of sIL-2R Measurements in Rheumatoid Arthritis and Cancers

2005 ◽  
Vol 2005 (3) ◽  
pp. 121-130 ◽  
Author(s):  
Anna Maria Witkowska
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Cells ◽  
T Lymphocyte ◽  
Biological Function ◽  
Current Knowledge ◽  
Lymphocyte Activation ◽  
Soluble Receptor ◽  
Disease Progress ◽  
Lines Of Evidence

A soluble IL-2 receptor (sIL-2R) is a circulating form of a membrane receptor localized on lymphoid and some cancer cells. The biological function of sIL-2R has not been completely understood. Substantially, it seems to reflect T-lymphocyte activation in diseases of different pathology. Moreover, the soluble receptor has been considered, at least in part, responsible for unsuccessful immunotherapy with IL-2 in cancers. Several lines of evidence indicate sIL-2R measurements to be useful in determining disease progress and prognosis. This review summarizes current knowledge on the sIL-2R behavior in RA and solid cancers of varied etiology.

The role of hypoxia in endometrial cancer

2021 ◽  
Vol 22 ◽  
Author(s):  
Yarely M. Salinas-Vera ◽  
Dolores Gallardo-Rincón ◽  
Erika Ruíz-García ◽  
Macrina B. Silva-Cázares ◽  
Carmen Sol de la Peña-Cruz ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Cell Survival ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Targeted Therapies ◽  
Current Knowledge ◽  
Vasculogenic Mimicry ◽  
Cellular Processes ◽  
Corpus Uteri

: Endometrial cancer represents the most frequent neoplasia from the corpus uteri, and comprises the 14th leading cause of death in women worldwide. Risk factors that contribute to the disease include early menarche, late menopause, nulliparity, and menopausal hormone use, as well as hypertension and obesity comorbidities. The clinical effectiveness of chemotherapy is variable, suggesting that novel molecular targeted therapies against specific cellular processes associated with the maintenance of cancer cell survival and therapy resistance urged to ameliorate the rates of success in endometrial cancer treatment. In the course of tumor growth, cancer cells must adapt to decreased oxygen availability in the microenvironment by upregulation of hypoxia-inducible factors, which orchestrate the activation of a transcriptional program leading to cell survival. During this adaptative process, the hypoxic cancer cells may acquire invasive and metastatic properties as well as increased cell proliferation and resistance to chemotherapy, enhanced angiogenesis, vasculogenic mimicry, and maintenance of cancer cell stemness, which contribute to more aggressive cancer phenotypes. Several studies have shown that hypoxia-inducible factor 1 alpha (HIF-1α) protein is aberrantly overexpressed in many solid tumors from breast, prostate, ovarian, bladder, colon, brain, and pancreas. Thus, it has been considered an important therapeutic target. Here, we reviewed the current knowledge of the relevant roles of cellular hypoxia mechanisms and HIF-1α functions in diverse processes associated with endometrial cancer progression. In addition, we also summarize the role of microRNAs in the posttranscriptional regulation of protein-encoding genes involved in the hypoxia response in endometrial cancer. Finally, we pointed out the need for urgent targeted therapies to impair the cellular processes activated by hypoxia in the tumor microenvironment.

scholarly journals The emerging role of mast cell proteases in asthma

2019 ◽  
Vol 54 (4) ◽  
pp. 1900685 ◽  
Author(s):  
Gunnar Pejler
Keyword(s):  
Mast Cell ◽  
Mast Cells ◽  
Current Knowledge ◽  
Secretory Granules ◽  
Cross Linking ◽  
Lysosomal Hydrolases ◽  
Ige Receptor ◽  
Deficient Mice ◽  
Lines Of Evidence

It is now well established that mast cells (MCs) play a crucial role in asthma. This is supported by multiple lines of evidence, including both clinical studies and studies on MC-deficient mice. However, there is still only limited knowledge of the exact effector mechanism(s) by which MCs influence asthma pathology. MCs contain large amounts of secretory granules, which are filled with a variety of bioactive compounds including histamine, cytokines, lysosomal hydrolases, serglycin proteoglycans and a number of MC-restricted proteases. When MCs are activated, e.g. in response to IgE receptor cross-linking, the contents of their granules are released to the exterior and can cause a massive inflammatory reaction. The MC-restricted proteases include tryptases, chymases and carboxypeptidase A3, and these are expressed and stored at remarkably high levels. There is now emerging evidence supporting a prominent role of these enzymes in the pathology of asthma. Interestingly, however, the role of the MC-restricted proteases is multifaceted, encompassing both protective and detrimental activities. Here, the current knowledge of how the MC-restricted proteases impact on asthma is reviewed.

scholarly journals Regulation of ST6GAL1 sialyltransferase expression in cancer cells

Glycobiology ◽  
2020 ◽  
Author(s):  
Kaitlyn A Dorsett ◽  
Michael P Marciel ◽  
Jihye Hwang ◽  
Katherine E Ankenbauer ◽  
Nikita Bhalerao ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Translational Regulation ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Sialic Acids ◽  
Invasion Resistance ◽  
Cell Behaviors ◽  
Molecular Events ◽  
Wide Range

Abstract The ST6GAL1 sialyltransferase, which adds α2–6 linked sialic acids to N-glycosylated proteins, is overexpressed in a wide range of human malignancies. Recent studies have established the importance of ST6GAL1 in promoting tumor cell behaviors such as invasion, resistance to cell stress, and chemoresistance. Furthermore, ST6GAL1 activity has been implicated in imparting cancer stem cell characteristics. However, despite the burgeoning interest in the role of ST6GAL1 in the phenotypic features of tumor cells, insufficient attention has been paid to the molecular mechanisms responsible for ST6GAL1 upregulation during neoplastic transformation. Evidence suggests that these mechanisms are multifactorial, encompassing genetic, epigenetic, transcriptional, and post-translational regulation. The purpose of this review is to summarize current knowledge regarding the molecular events that drive enriched ST6GAL1 expression in cancer cells.

scholarly journals Beverages in Rheumatoid Arthritis: What to Prefer or to Avoid

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3155 ◽  
Author(s):  
Mrinalini Dey ◽  
Maurizio Cutolo ◽  
Elena Nikiphorou
Keyword(s):  
Rheumatoid Arthritis ◽  
Patient Management ◽  
Current Knowledge ◽  
Signalling Pathways ◽  
Main Body ◽  
Future Studies ◽  
Downstream Effects ◽  
Controversial Topic ◽  
Diet And Lifestyle

Background: The role of nutrition in the pathogenesis of rheumatic diseases, including rheumatoid arthritis (RA), has gained increasing attention in recent years. A growing number of studies have focussed on the diverse nutritional contents of beverages, and their possible role in the development and progression of RA. Main body: We aimed to summarise the current knowledge on the role of a range of beverages in the context of RA. Beverages have a key role within the mosaic of autoimmunity in RA and potential to alter the microbiome, leading to downstream effects on inflammatory pathways. The molecular contents of beverages, including coffee, tea, and wine, have similarly been found to interfere with immune signalling pathways, some beneficial for disease progression and others less so. Finally, we consider beverages in the context of wider dietary patterns, and how this growing body of evidence may be harnessed by the multidisciplinary team in patient management. Conclusions: While there is increasing work focussing on the role of beverages in RA, integration of discussions around diet and lifestyle in our management of patients remains sparse. Nutrition in RA remains a controversial topic, but future studies, especially on the role of beverages, are likely to shed further light on this in coming years.

Hepcidin: A Clue for a New Role for Lymphocytes.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1999-1999
Author(s):  
Jorge P Pinto ◽  
Vera Dias ◽  
Heinz Zoller ◽  
Pedro N Rodrigues ◽  
Helena Carmo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Iron Overload ◽  
T Lymphocyte ◽  
Peripheral Blood ◽  
Lymphocyte Activation ◽  
Peripheral Blood Lymphocytes ◽  
Ferric Citrate ◽  
Intracellular Iron ◽  
Hepcidin Expression

Abstract Abstract 1999 Poster Board I-1021 Background: Recent evidence suggests the involvement of lymphocytes in the severity of iron overload disorders, with increased severity of iron overload in Hereditary Hemochromatosis patients and in animal models with lymphocyte number deficiencies. However, no mechanism(s) has been suggested to explain these observations. The aim of this study was to analyze hepcidin expression in lymphocytes. Methods: Expression of hepcidin was analyzed by Real-time PCR in human and mouse Peripheral Blood Lymphocytes (PBLs) and in selected resting lymphocyte populations, in response to holotransferrin and ferric citrate. The effect of hepcidin in the expression of the iron exporter Ferroportin was analyzed by FACS and confocal immunofluorescence. Cellular iron traffic was analyzed by measurement of 55Fe and 125I-TF, cell proliferation assessed by BrdU incorporation and silencing of gene expression in lymphocytes performed with siRNAs. Results: Hepcidin is expressed in PBLs and is up-regulated in response to holotransferrin and ferric citrate. The response to holotransferrin was observed in CD8+ and not in CD4+ lymphocytes, a result confirmed by the failure of lymphocytes from β2-microglobulin-KO mice to respond to holotransferrin, in comparison with Bl6/J controls. Hepcidin up-regulation induced by holotransferrin decreases ferroportin expression, inducing its co-localization with the proteasome marker LMP2. Tumor Necrosis Factor-á (TNF-á) expression in PBLs increases with holotransferrin treatments. siRNA-mediated silencing of TNF-á in PBLs abrogates hepcidin up-regulation by holotransferrin and incubation of PBLs with recombinant TNF-á increases hepcidin expression, suggesting the involvement of this cytokine in the basal and holotransferrin-induced hepcidin expression in these cells. The role of hepcidin in a situation of high iron demand - lymphocyte activation and proliferation - was assessed. Hepcidin expression increases with T-lymphocyte activation and siRNA-mediated silencing of hepcidin in activated T lymphocytes causes a decrease in intracellular iron levels, by increasing ferroportin-mediated iron export. The low intracellular iron levels were associated with impaired T lymphocyte proliferation. Discussion: The ability of PBLs to increase hepcidin expression in response to ferric citrate distinguishes lymphocytes from hepatocytes and places peripheral blood lymphocyte numbers as a first line of response to increases in transferrin saturation and presence of NTBI, characteristic of iron overload disorders. The findings that hepcidin modulates ferroportin expression, intracellular iron levels and cell proliferation in lymphocytes demonstrate the importance of this protein for lymphocyte iron homeostasis. The control of the intracellular iron levels of lymphocytes confers to hepcidin a pivotal role in the postulated ability of circulating lymphocytes to function as “biological iron chelators”. Conclusion: With the demonstration, for the first time, of hepcidin synthesis by peripheral blood lymphocytes, of its regulation by elemental iron and of its involvement in T cell proliferation, the present results put forward a molecular mechanism for the described modifier role of lymphocytes in protection from iron toxicity. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Role of Poly(ADP-ribose) Polymerase-1 in Rheumatoid Arthritis

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Samuel García ◽  
Carmen Conde
Keyword(s):  
Rheumatoid Arthritis ◽  
Septic Shock ◽  
Dna Repair ◽  
Beneficial Effect ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Genomic Stability ◽  
Inflammatory Processes ◽  
Parp 1

Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme with a crucial role in the maintenance of genomic stability. In addition to the role of PARP-1 in DNA repair, multiple studies have also demonstrated its involvement in several inflammatory diseases, such as septic shock, asthma, atherosclerosis, and stroke, as well as in cancer. In these diseases, the pharmacological inhibition of PARP-1 has shown a beneficial effect, suggesting that PARP-1 regulates their inflammatory processes. In recent years, we have studied the role of PARP-1 in rheumatoid arthritis, as have other researchers, and the results have shown that PARP-1 has an important function in the development of this disease. This review summarizes current knowledge on the effects of PARP-1 in rheumatoid arthritis.

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