scholarly journals Targeting Protein Kinases in Blood Cancer: Focusing on CK1α and CK2

2021 ◽  
Vol 22 (7) ◽  
pp. 3716
Author(s):  
Zaira Spinello ◽  
Anna Fregnani ◽  
Laura Quotti Tubi ◽  
Livio Trentin ◽  
Francesco Piazza ◽  
...  
Keyword(s):  
Tyrosine Kinases ◽  
Current Data ◽  
Protein Kinase Activity ◽  
Biological Processes ◽  
Oncogene Addiction ◽  
Gene Encoding ◽  
Cancer Hallmarks ◽  
Hematological Cancers ◽  
Different Types ◽  
Kinase Phosphorylation

Disturbance of protein kinase activity may result in dramatic consequences that often lead to cancer development and progression. In tumors of blood origin, both tyrosine kinases and serine/threonine kinases are altered by different types of mutations, critically regulating cancer hallmarks. CK1α and CK2 are highly conserved, ubiquitously expressed and constitutively active pleiotropic kinases, which participate in multiple biological processes. The involvement of these kinases in solid and blood cancers is well documented. CK1α and CK2 are overactive in multiple myeloma, leukemias and lymphomas. Intriguingly, they are not required to the same degree for the viability of normal cells, corroborating the idea of “druggable” kinases. Different to other kinases, mutations on the gene encoding CK1α and CK2 are rare or not reported. Actually, these two kinases are outside the paradigm of oncogene addiction, since cancer cells’ dependency on these proteins resembles the phenomenon of “non-oncogene” addiction. In this review, we will summarize the general features of CK1α and CK2 and the most relevant oncogenic and stress-related signaling nodes, regulated by kinase phosphorylation, that may lead to tumor progression. Finally, we will report the current data, which support the positioning of these two kinases in the therapeutic scene of hematological cancers.

Nanoparticles Functionalized with Venom-Derived Peptides and Toxins for Pharmaceutical Applications

2020 ◽  
Vol 21 (2) ◽  
pp. 97-109 ◽  
Author(s):  
Ana P. dos Santos ◽  
Tamara G. de Araújo ◽  
Gandhi Rádis-Baptista
Keyword(s):  
Oral Absorption ◽  
Current Data ◽  
Pharmacological Activities ◽  
Venom Peptides ◽  
Essential Components ◽  
Wide Range ◽  
Different Types ◽  
Direct Use ◽  
Animal Venoms ◽  
Pharmaceutical Biotechnology

Venom-derived peptides display diverse biological and pharmacological activities, making them useful in drug discovery platforms and for a wide range of applications in medicine and pharmaceutical biotechnology. Due to their target specificities, venom peptides have the potential to be developed into biopharmaceuticals to treat various health conditions such as diabetes mellitus, hypertension, and chronic pain. Despite the high potential for drug development, several limitations preclude the direct use of peptides as therapeutics and hamper the process of converting venom peptides into pharmaceuticals. These limitations include, for instance, chemical instability, poor oral absorption, short halflife, and off-target cytotoxicity. One strategy to overcome these disadvantages relies on the formulation of bioactive peptides with nanocarriers. A range of biocompatible materials are now available that can serve as nanocarriers and can improve the bioavailability of therapeutic and venom-derived peptides for clinical and diagnostic application. Examples of isolated venom peptides and crude animal venoms that have been encapsulated and formulated with different types of nanomaterials with promising results are increasingly reported. Based on the current data, a wealth of information can be collected regarding the utilization of nanocarriers to encapsulate venom peptides and render them bioavailable for pharmaceutical use. Overall, nanomaterials arise as essential components in the preparation of biopharmaceuticals that are based on biological and pharmacological active venom-derived peptides.

Functional Role of p38 Mitogen Activated Protein Kinase in Platelet Activation induced by a Thromboxane A2 Analogue and by 8-iso-prostaglandin F2 α

2002 ◽  
Vol 87 (05) ◽  
pp. 888-898 ◽  
Author(s):  
Stefania Gaino ◽  
Valeria Zuliani ◽  
Rosa Tommasoli ◽  
Donatella Benati ◽  
Riccardo Ortolani ◽  
...  
Keyword(s):  
Map Kinase ◽  
Platelet Activation ◽  
Tyrosine Kinases ◽  
Actin Polymerization ◽  
Shape Change ◽  
Specific Inhibitor ◽  
P38 Map Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Kinase Phosphorylation

SummaryWe investigated similarities in the signaling pathways elicited by the F2 isoprostane 8-iso-PGF2α and by low doses of U46619 to induce platelet activation. Both 0.01-0.1 µmol/L U46619 and 0.01-1 µmol/L 8-isoPGF2α triggered shape change and filopodia extension, as well as adhesion to immobilized fibrinogen of washed platelets. At these doses the two platelet agonists failed to trigger secretion and aggregation, which were however induced by higher doses of U46619 (0.1-1 µmol/L). SB203580 (1-10 µmol/L), a specific inhibitor of the p38 mitogen activated protein (MAP) kinase blunted platelet shape change and adhesion induced by 0.05-1 µmol/L 8-iso-PGF2α and by 0.01 µmol/L U46619. These platelet responses were also inhibited by 20 µmol/L cytochalasin D, an inhibitor of actin polymerization, and 50 µmol/L piceatannol, an inhibitor of the Syk tyrosine kinases. Both 8-iso-PGF2α and U46619-induced p38 MAP kinase phosphorylation in suspended platelets and this was inhibited by piceatannol, indicating that Syk activation occurs upstream p38 MAP kinase phosphorylation. These findings suggest that the signaling pathway triggered by both 8-iso-PGF2α and low concentrations of U46619 to induce platelet adhesion and shape change implicates Syk, the p38 MAP kinase, and actin polymerization.

scholarly journals The Role of Non-Coding RNAs in the Regulation of the Proto-Oncogene MYC in Different Types of Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 921
Author(s):  
Ekaterina Mikhailovna Stasevich ◽  
Matvey Mikhailovich Murashko ◽  
Lyudmila Sergeevna Zinevich ◽  
Denis Eriksonovich Demin ◽  
Anton Markovich Schwartz
Keyword(s):  
Malignant Tumors ◽  
Current Data ◽  
Cellular Processes ◽  
Cell Divisions ◽  
Specific Tumor ◽  
Different Types ◽  
Myc Gene ◽  
Non Coding Rnas ◽  
Tumor Types

Alterations in the expression level of the MYC gene are often found in the cells of various malignant tumors. Overexpressed MYC has been shown to stimulate the main processes of oncogenesis: uncontrolled growth, unlimited cell divisions, avoidance of apoptosis and immune response, changes in cellular metabolism, genomic instability, metastasis, and angiogenesis. Thus, controlling the expression of MYC is considered as an approach for targeted cancer treatment. Since c-Myc is also a crucial regulator of many cellular processes in healthy cells, it is necessary to find ways for selective regulation of MYC expression in tumor cells. Many recent studies have demonstrated that non-coding RNAs play an important role in the regulation of the transcription and translation of this gene and some RNAs directly interact with the c-Myc protein, affecting its stability. In this review, we summarize current data on the regulation of MYC by various non-coding RNAs that can potentially be targeted in specific tumor types.

scholarly journals Reversing resistance: different routes and common themes across pathogens

2017 ◽  
Vol 284 (1863) ◽  
pp. 20171619 ◽  
Author(s):  
Richard C. Allen ◽  
Jan Engelstädter ◽  
Sebastian Bonhoeffer ◽  
Bruce A. McDonald ◽  
Alex R. Hall
Keyword(s):  
Fitness Cost ◽  
Biological Processes ◽  
Short Supply ◽  
Compensatory Evolution ◽  
Wide Range ◽  
Different Types ◽  
Cost Of Resistance

Resistance spreads rapidly in pathogen or pest populations exposed to biocides, such as fungicides and antibiotics, and in many cases new biocides are in short supply. How can resistance be reversed in order to prolong the effectiveness of available treatments? Some key parameters affecting reversion of resistance are well known, such as the fitness cost of resistance. However, the population biological processes that actually cause resistance to persist or decline remain poorly characterized, and consequently our ability to manage reversion of resistance is limited. Where do susceptible genotypes that replace resistant lineages come from? What is the epidemiological scale of reversion? What information do we need to predict the mechanisms or likelihood of reversion? Here, we define some of the population biological processes that can drive reversion, using examples from a wide range of taxa and biocides. These processes differ primarily in the origin of revertant genotypes, but also in their sensitivity to factors such as coselection and compensatory evolution that can alter the rate of reversion, and the likelihood that resistance will re-emerge upon re-exposure to biocides. We therefore argue that discriminating among different types of reversion allows for better prediction of where resistance is most likely to persist.

scholarly journals TCF12 controls oligodendroglial cell proliferation and regulates signaling pathways conserved in gliomas

2021 ◽  
Author(s):  
Sofia Archontidi ◽  
Corentine Marie ◽  
Beata Gyorgy ◽  
Justine Guegan ◽  
Marc Sanson ◽  
...  
Keyword(s):  
Biological Processes ◽  
Oligodendrocyte Differentiation ◽  
Gene Encoding ◽  
Genome Wide ◽  
Diffuse Gliomas ◽  
Mrna And Protein Expression ◽  
Oligodendrocyte Precursor ◽  
Oligodendrocyte Development ◽  
Chromatin Profiling

Diffuse gliomas are primary brain tumors originating from the transformation of glial cells. In particular, oligodendrocyte precursor cells constitute the major tumor-amplifying population in the gliomagenic process. We previously identified the TCF12 gene, encoding a transcription factor of the E protein family, as being recurrently mutated in oligodendrogliomas. In this study, we sought to understand the function of TCF12 in oligodendroglial cells, the glioma lineage of origin. We first describe TCF12 mRNA and protein expression pattern in oligodendroglial development in the mouse brain. Second, by TCF12 genome wide chromatin profiling in oligodendroglial cells, we show that TCF12 binds active promoters of genes involved in proliferation, translation/ribosomes, and pathways involved in oligodendrocyte development and cancer. Finally, we perform OPC-specific Tcf12 inactivation in vivo and demonstrate by immunofluorescence and transcriptomic analyses that TCF12 is transiently required for OPC proliferation but dispensable for oligodendrocyte differentiation. We further show that Tcf12 inactivation results in deregulation of biological processes that are also altered in oligodendrogliomas. Together, our data suggest that TCF12 directly regulates transcriptional programs in oligodendroglia development that are relevant in a glioma context.

scholarly journals The 3’UTR of the orb2 gene encoding the Drosophila CPEB translation factor plays a critical role in spermatogenesis

2020 ◽  
Author(s):  
Rudolf A. Gilmutdinov ◽  
Eugene N. Kozlov ◽  
Ludmila V. Olenina ◽  
Alexei A. Kotov ◽  
Justinn Barr ◽  
...  
Keyword(s):  
Deletion Mutant ◽  
Critical Role ◽  
Self Regulation ◽  
Biological Processes ◽  
Apparent Effect ◽  
Gene Encoding ◽  
Cytoplasmic Polyadenylation ◽  
Polarized Cells ◽  
Biological Context

AbstractCPEB proteins are conserved translation regulators involved in multiple biological processes. One of these proteins in Drosophila, Orb2, is a principal player in spermatogenesis. It is required for meiosis and spermatid differentiation. During the later process orb2 mRNAs and proteins are localized within the developing spermatid. To evaluate the role of orb2 mRNA 3’UTR in spermatogenesis, we used the CRISPR/Cas9 system to generate a deletion of the orb2 3’UTR, orb2R. This deletion disrupts the process of spermatid differentiation, but has no apparent effect on meiosis. While this deletion appears to destabilize the orb2 mRNA and reduce the levels of Orb2 protein, this is not the primary cause of the differentiation defects. Instead, differentiation appears to be disrupted because orb2 mRNAs and proteins are not properly localized within the differentiating spermatids. Other transcripts and proteins involved in spermatogenesis are also mislocalized in orb2R spermatids.Author summaryThe conserved family of cytoplasmic polyadenylation element binding (CPEB) proteins can activate or repress translation of target mRNAs, depending on the specific biological context, through interaction with special cytoplasmic polyadenylation element (CPE) sequences. These proteins function mainly in highly polarized cells. Orb2, one of the two Drosophila melanogaster CPEB proteins, is predominantly expressed in the testes and is crucial for spermatogenesis. The 3’UTR of orb2 transcript contains multiple CPE-like motifs, which is indicative of orb2 self-regulation. We have generated a deletion that removes the greater portion of 3’UTR. While this deletion causes a reduction in the levels of orb2 mRNA and the protein, this does not appear to be responsible for the defects in spermatogenesis observed in the deletion mutant. Instead, it is the mislocalization of the mRNA and protein in the developing spermatids.

Simulations in orthopedics and rehabilitation – Part I: Simulators

2016 ◽  
Vol 12 (4) ◽  
Author(s):  
Jacek Dygut ◽  
Piotr Piwowar ◽  
Maria Gołda ◽  
Krzysztof Popławski ◽  
Robert Jakubas ◽  
...  
Keyword(s):  
Computer Simulation ◽  
The Other ◽  
Fine Tuning ◽  
Patient Treatment ◽  
Biological Processes ◽  
Clinical Environment ◽  
Knowledge And Skills ◽  
Simulation Techniques ◽  
Resident Physicians ◽  
Different Types

AbstractNowadays, medical simulators and computer simulation programs are used to train various skills required in medicine. The development of medicine, including orthopedics and rehabilitation, has meant that resident physicians, within a much shorter period of time, must acquire the knowledge and skills that their older colleagues gained over years, learning as they operated on patients. For this reason, simulation very often helps the doctor and others engaged in health care train some techniques necessary during the work before they start working in a clinical environment. They have a chance of fine-tuning certain skills under nonclinical environment. On the other hand, simulation techniques are used in medical scientific research to know and explain the different biological processes that can be used for better patient treatment in the future. In this paper (Part I), the authors focused on the presentation of different types of simulators for the following purposes: test (conducted under laboratory conditions), training (incorporated into school, universities syllabus), diagnostic and therapeutic (within the hospital, clinics, private medical practice).

scholarly journals Epigenetic modifications of histones in cancer

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Zibo Zhao ◽  
Ali Shilatifard
Keyword(s):  
Histone Modifications ◽  
Functional Significance ◽  
Epigenetic Modifications ◽  
Cancer Development ◽  
Clinical Implications ◽  
Biological Processes ◽  
Disease Pathogenesis ◽  
Different Types ◽  
Histone Modifiers ◽  
The Many

AbstractThe epigenetic modifications of histones are versatile marks that are intimately connected to development and disease pathogenesis including human cancers. In this review, we will discuss the many different types of histone modifications and the biological processes with which they are involved. Specifically, we review the enzymatic machineries and modifications that are involved in cancer development and progression, and how to apply currently available small molecule inhibitors for histone modifiers as tool compounds to study the functional significance of histone modifications and their clinical implications.

scholarly journals Dissimilar mechanisms of Ca2+response to bradykinin in different types of juxtamedullary glomerular arterioles

1999 ◽  
Vol 277 (5) ◽  
pp. F697-F705 ◽  
Author(s):  
F. Praddaude ◽  
J. Marchetti ◽  
F. Alhenc-Gelas ◽  
J.-L. Ader
Keyword(s):  
Tyrosine Kinases ◽  
Maximal Response ◽  
Lower Sensitivity ◽  
Free Medium ◽  
Herbimycin A ◽  
Intracellular Calcium Level ◽  
Different Types ◽  
Intracellular Ca ◽  
Induced Changes ◽  
Glomerular Arterioles

Bradykinin (BK)-induced changes in intracellular calcium level ([Ca2+]i) were studied on fura 2-loaded afferent (AA) and efferent glomerular arterioles (EA) microdissected from juxtamedullary renal cortex. A distinction was made between thin and muscular EA. In AA and both types of EA, BK increased [Ca2+]ithrough activation of B2 receptors located only on the endothelium. The responses were not affected by nifedipine (10−6 M) and were smaller in a Ca2+-free medium, providing evidence that BK opens voltage-independent Ca2+ channels and mobilizes intracellular Ca2+. Thin EA differed from AA and muscular EA by a lower sensitivity to BK (EC50 = 6.95 ± 3.81 vs. 0.21 ± 0.08 and 0.18 ± 0.13 nM, respectively; P < 0.05), a higher maximal response (89 ± 5 vs. 57 ± 5 and 44 ± 7 nM; P < 0.001), and a spontaneous return to basal Ca2+ level, even in the presence of BK. Genistein (10−4 M) and herbimycin A (25 × 10−6M), specific inhibitors of tyrosine kinases, inhibited the [Ca2+]iresponses exclusively in AA. Genistein reduced the peak and plateau phases of responses by 69 ± 9 and 82 ± 6%, respectively, in a medium with Ca2+ and the peak by 48 ± 9% in a Ca2+-free medium. Similar reductions were observed with herbimycin A. These results show that dissimilar signal transduction pathways are involved in BK effects on juxtamedullary arterioles and that a tyrosine kinase activity could participate in the regulation of BK effect on AA but not on EA.

scholarly journals Flavonoids and Isoflavonoids Biosynthesis in the Model Legume Lotus japonicus; Connections to Nitrogen Metabolism and Photorespiration

Plants ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 774 ◽  
Author(s):  
Margarita García-Calderón ◽  
Carmen M. Pérez-Delgado ◽  
Peter Palove-Balang ◽  
Marco Betti ◽  
Antonio J. Márquez
Keyword(s):  
Abiotic Stress ◽  
Nitrogen Metabolism ◽  
Lotus Japonicus ◽  
Regulatory Proteins ◽  
Phenylpropanoid Metabolism ◽  
Biological Processes ◽  
Model Legume ◽  
Different Types ◽  
Made In

Phenylpropanoid metabolism represents an important metabolic pathway from which originates a wide number of secondary metabolites derived from phenylalanine or tyrosine, such as flavonoids and isoflavonoids, crucial molecules in plants implicated in a large number of biological processes. Therefore, various types of interconnection exist between different aspects of nitrogen metabolism and the biosynthesis of these compounds. For legumes, flavonoids and isoflavonoids are postulated to play pivotal roles in adaptation to their biological environments, both as defensive compounds (phytoalexins) and as chemical signals in symbiotic nitrogen fixation with rhizobia. In this paper, we summarize the recent progress made in the characterization of flavonoid and isoflavonoid biosynthetic pathways in the model legume Lotus japonicus (Regel) Larsen under different abiotic stress situations, such as drought, the impairment of photorespiration and UV-B irradiation. Emphasis is placed on results obtained using photorespiratory mutants deficient in glutamine synthetase. The results provide different types of evidence showing that an enhancement of isoflavonoid compared to standard flavonol metabolism frequently occurs in Lotus under abiotic stress conditions. The advance produced in the analysis of isoflavonoid regulatory proteins by the use of co-expression networks, particularly MYB transcription factors, is also described. The results obtained in Lotus japonicus plants can be also extrapolated to other cultivated legume species, such as soybean, of extraordinary agronomic importance with a high impact in feeding, oil production and human health.

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