scholarly journals Can NF-κB Be Considered a Valid Drug Target in Neoplastic Diseases? Our Point of View

2020 ◽  
Vol 21 (9) ◽  
pp. 3070 ◽  
Author(s):  
Manuela Labbozzetta ◽  
Monica Notarbartolo ◽  
Paola Poma

Multidrug resistance (MDR), of the innate and acquired types, is one of major problems in treating tumor diseases with a good chance of success. In this review, we examine the key role of nuclear factor-kappa B (NF-κB) to induce MDR in three tumor models characterized precisely by innate or acquired MDR, in particular triple negative breast cancer (TNBC), hepatocellular carcinoma (HCC), and acute myeloid leukemia (AML). We also present different pharmacological approaches that our group have employed to reduce the expression/activation of this transcriptional factor and thus to restore chemo-sensitivity. Finally, we examine the latest scientific evidence found by other groups, the most significant clinical trials regarding NF-κB, and new perspectives on the possibility to consider this transcriptional factor a valid drug target in neoplastic diseases.

2015 ◽  
Vol 10s3 ◽  
pp. BMI.S22432 ◽  
Author(s):  
Il-Kang Na ◽  
Philipple Coutre

Tyrosine kinases (TKs) play a significant role in cancerogenesis and cancer cell function. Initial developments in this field go back to the early 80s, but the success story really started with the selective BCR-ABL inhibitor, imatinib. Owing to the cancer-driving role of BCR-ABL in chronic myeloid leukemia (CML), excellent response rates lead to fast FDA approval in both the first and second treatments of CML patients. Since then, numerous TKs were identified. TK inhibitors have been developed accordingly, and technology to test for ideal drug–target interactions has profoundly improved. By now, medical oncologists and hematologists struggle to have a pool of potential TK inhibitors, where the most efficient one could be picked out to treat a specific cancer patient, which might also help overcome the occurring resistance mechanisms against TK inhibitors. Whether disease eradication can be achieved via single or sequential TK inhibitor treatment(s) needs to be tested in the present and in the future.


2021 ◽  
Vol 51 (3) ◽  
Author(s):  
Alberto Caminero

It is estimated that around 25% of the population worldwide experience adverse reactions to food, which are very diverse based on both etiology and clinical presentation. According to the pathophysiological processes involved, adverse reactions to foods can be broadly classified as sensitivities or intolerances, depending on whether they are immune-mediated, or not. Specifically, food sensitivities have become a growing clinical, economic, and social problem nowadays. Although the reason for the increased prevalence of well-determined food sensitives such as celiac disease and food allergies is not well understood, the role of microbes in both inducing and protecting from these conditions has been proposed. First, several studies suggest that the gut microbiota, the vast number of microbes that live in our digestive tract, influence the appearance of different adverse reactions to food. These studies are based on observational changes in the composition and function of the fecal microbiota of celiac, allergic and food intolerant patients when compared to controls or healthy participants. Second, infectious microbial agents have been related to the loss of oral tolerance towards dietary components and the occurrence of different adverse reactions to foods. However, how could microbes participate in food sensitivities and intolerances from a mechanistic point of view? Preclinical studies with animal models not only support observations in humans, they also show a causal role of microbes in the occurrence and course of these diseases, while informing the specific underlying mechanisms. The aim of this review is to summarize the scientific evidence that supports the role of microbes in the main adverse reactions to food described, with an emphasis on the underlying mechanisms. The discovery of the main molecular pathways involved in pathogenic reactions to diet foods will accelerate the development of new therapeutic approaches with the aim of preventing and treating food sensitivities and intolerances.


Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 43
Author(s):  
Maria V. Yusenko ◽  
Abhiruchi Biyanee ◽  
Daria Frank ◽  
Leonhard H. F. Köhler ◽  
Mattias K. Andersson ◽  
...  

Studies of the role of MYB in human malignancies have highlighted MYB as a potential drug target for acute myeloid leukemia (AML) and adenoid cystic carcinoma (ACC). Here, we present the initial characterization of 2-amino-4-(3,4,5-trimethoxyphenyl)-4H-naphtho[1,2-b]pyran-3-carbonitrile (Bcr-TMP), a nanomolar-active MYB-inhibitory compound identified in a screen for novel MYB inhibitors. Bcr-TMP affects MYB function in a dual manner by inducing its degradation and suppressing its transactivation potential by disrupting its cooperation with co-activator p300. Bcr-TMP also interferes with the p300-dependent stimulation of C/EBPβ, a transcription factor co-operating with MYB in myeloid cells, indicating that Bcr-TMP is a p300-inhibitor. Bcr-TMP reduces the viability of AML cell lines at nanomolar concentrations and induces cell-death and expression of myeloid differentiation markers. It also down-regulates the expression of MYB target genes and exerts stronger anti-proliferative effects on MYB-addicted primary murine AML cells and patient-derived ACC cells than on their non-oncogenic counterparts. Surprisingly, we observed that Bcr-TMP also has microtubule-disrupting activity, pointing to a possible link between MYB-activity and microtubule stability. Overall, Bcr-TMP is a highly potent multifunctional MYB-inhibitory agent that warrants further investigation of its therapeutic potential and mechanism(s) of action.


Author(s):  
N.V. Belov ◽  
U.I. Papiashwili ◽  
B.E. Yudovich

It has been almost universally adopted that dissolution of solids proceeds with development of uniform, continuous frontiers of reaction.However this point of view is doubtful / 1 /. E.g. we have proved the active role of the block (grain) boundaries in the main phases of cement, these boundaries being the areas of hydrate phases' nucleation / 2 /. It has brought to the supposition that the dissolution frontier of cement particles in water is discrete. It seems also probable that the dissolution proceeds through the channels, which serve both for the liquid phase movement and for the drainage of the incongruant solution products. These channels can be appeared along the block boundaries.In order to demonsrate it, we have offered the method of phase-contrast impregnation of the hardened cement paste with the solution of methyl metacrylahe and benzoyl peroxide. The viscosity of this solution is equal to that of water.


2019 ◽  
Vol 89 (1-2) ◽  
pp. 80-88 ◽  
Author(s):  
Juliana Soares Severo ◽  
Jennifer Beatriz Silva Morais ◽  
Taynáh Emannuelle Coelho de Freitas ◽  
Ana Letícia Pereira Andrade ◽  
Mayara Monte Feitosa ◽  
...  

Abstract. Thyroid hormones play an important role in body homeostasis by facilitating metabolism of lipids and glucose, regulating metabolic adaptations, responding to changes in energy intake, and controlling thermogenesis. Proper metabolism and action of these hormones requires the participation of various nutrients. Among them is zinc, whose interaction with thyroid hormones is complex. It is known to regulate both the synthesis and mechanism of action of these hormones. In the present review, we aim to shed light on the regulatory effects of zinc on thyroid hormones. Scientific evidence shows that zinc plays a key role in the metabolism of thyroid hormones, specifically by regulating deiodinases enzymes activity, thyrotropin releasing hormone (TRH) and thyroid stimulating hormone (TSH) synthesis, as well as by modulating the structures of essential transcription factors involved in the synthesis of thyroid hormones. Serum concentrations of zinc also appear to influence the levels of serum T3, T4 and TSH. In addition, studies have shown that Zinc transporters (ZnTs) are present in the hypothalamus, pituitary and thyroid, but their functions remain unknown. Therefore, it is important to further investigate the roles of zinc in regulation of thyroid hormones metabolism, and their importance in the treatment of several diseases associated with thyroid gland dysfunction.


2001 ◽  
Vol 28 (6) ◽  
pp. 626-633 ◽  
Author(s):  
James R. Berenson ◽  
Hongjin M. Ma ◽  
Robert Vescio

2009 ◽  
pp. 4-27
Author(s):  
A. Cohen ◽  
G. Harcourt

The article written by the well-known theorists and historians of economic thought contains a detailed overview of the Cambridge capital controversy, which had raged from the mid-1950-s through the mid-1970-s. The authors track the origins of the controversy and cover arguments of both sides in chronological order. From their point of view, the discussion hasnt been resolved, and its main underlying aspects were ideological beliefs and fundamental methodological controversies on the nature of equilibrium and on the role of time in economic theory. The article is published with comments written by other leading theoreticians.


2019 ◽  
pp. 22-29
Author(s):  
Н. В. Фрадкіна

The purpose and tasks of the work are to analyze the contemporary Ukrainian mass culture in terms of its value and humanistic components, as well as the importance of cultural studies and Ukrainian studies in educational disciplines for the formation of a holistic worldview of modern youth.Analysis of research and publications. Scientists repeatedly turned to the problems of the role of spirituality in the formation of society and its culture. This problem is highlighted in the publications by O. Losev, V. Lytvyn, D. Likhachev, S. Avierintsev, M. Zakovych, I. Stepanenko and E. Kostyshyn.Experts see the main negative impact of mass culture on the quality approach, which determines mass culture through the market, because mass culture, from our point of view, is everything that is sold and used in mass demand.One of the most interesting studies on this issue was the work by the representatives of Frankfurt School M. Horkheimer and T. Adorno «Dialectics of Enlightenment» (1947), devoted to a detailed analysis of mass culture. Propaganda at all socio-cultural levels in the form is similar in both totalitarian and democratic countries. It is connected, according to the authors, with the direction of European enlightenment. The tendency to unify people is a manifestation of the influence of mass culture, from cinema to pop. Mass culture is a phenomenon whose existence is associated with commerce (accumulation in any form – this is the main feature of education), in general, the fact that it exists in this form is related to the direction of the history of civilization.Modern mass culture, with its externally attractive and easily assimilated ideas and symbols, appealing to the trends of modern fashion, becomes a standard of prestigious consumption, does not require intense reflection, allows you to relax, distract, not teach, but entertains, preaches hedonism as the main spiritual value. And as a consequence, there are socio-cultural risks: an active rejection of other people, which leads to the formation of indifference; cruelty as a character trait; increase of violent and mercenary crime; increase in the number of alcohol and drug addicts; anti-patriotism; indifference to the values of the family and as a result of social orphanhood and prostitution.Conclusions, perspectives of research. Thus, we can conclude that modern Ukrainian education is predominantly formed by the values of mass culture. Namely, according to the «Dialectic» by Horkheimer and Adorno, «semi-enlightenment becomes an objective spirit» of our modern society.It is concluded that only high-quality education can create the opposite of the onset of mass culture and the destruction of spirituality in our society. It is proved that only by realizing the importance of cultivating disciplines in the educational process and the spiritual upbringing of the nation, through educational reforms, humanitarian knowledge will gradually return to student audiences.Formation of youth occurs under the influence of social environment, culture, education and self-education. The optimal combination of these factors determines both the process of socialization itself and how successful it will be. In this context, one can see the leading role of education and upbringing. It turns out that the main task of modern education is to spread its influence on the development of spiritual culture of the individual, which eventually becomes a solid foundation for the formation of the individual. Such a subject requires both philosophical and humanitarian approaches in further integrated interdisciplinary research, since the availability of such research will provide the theoretical foundation for truly modern educational and personal development.


2020 ◽  
pp. 75-79
Author(s):  
R. M. Gambarova

Relevance. Grain is the key to strategic products to ensure food security. From this point of view, the creation of large grain farms is a matter for the country's selfsufficiency and it leading to a decrease in financial expense for import. Creation of such farms creates an abundance of productivity from the area and leads to obtaining increased reproductive seeds. The main policy of the government is to minimize dependency from import, create abundance of food and create favorable conditions for export potential.The purpose of the study: the development of grain production in order to ensure food security of the country and strengthen government support for this industry.Methods: comparative analysis, systems approach.Results. As shown in the research, if we pay attention to the activities of private entrepreneurship in the country, we can see result of the implementation of agrarian reforms after which various types of farms have been created in republic.The role of privateentrepreneurshipinthedevelopmentofproduction is great. Тhe article outlines the sowing area, production, productivity, import, export of grain and the level of selfsufficiency in this country from 2015 till 2017.


2019 ◽  
Vol 16 (2-3) ◽  
pp. 161-179
Author(s):  
Outi Paloposki

The article looks at book production and circulation from the point of view of translators, who, as purchasers and readers of foreign-language books, are an important mediating force in the selection of literature for translation. Taking the German publisher Tauchnitz's series ‘Collection of British Authors’ and its circulation in Finland in the nineteenth and early twentieth century as a case in point, the article argues that the increased availability of English-language books facilitated the acquiring and honing of translators' language skills and gradually diminished the need for indirect translating. Book history and translation studies meet here in an examination of the role of the Collection in Finnish translators' work.


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