Neda Pintarić, Ivana Čagalj i Ivana Vidović Bolt. (ur.) Komparativnoslavističke lingvokulturalne teme. Srednja Europa, Zagreb, 2019., 409 str.

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Controversy about pharmacological modulation of Nrf2 for cancer therapy

Conventional anticancer therapies such as radiotherapy and chemotherapies are associated with oxidative stress generating reactive oxygen species (ROS) and reactive aldehydes like 4-hydroxynonenal in cancer cells that govern them to die. The main mechanism activated due to exposure of the cell to these reactive species is the Nrf2-Keap1 pathway. Although Nrf2 was firstly perceived as a tumor suppressor that inhibits tumor initiation and cancer metastasis, more recent data reveal its role also as a pro-oncogenic factor. Discovery of the upregulation of Nrf2 in different types of cancer supports such undesirable pathophysiological roles of Nrf2. The upregulation of Nrf2 leads to activation of cytoprotective genes thus helping malignant cells to withstand high levels of ROS and to avoid apoptosis, eventually becoming resistant to conventional anticancer therapy. Therefore, new treatment strategies are needed for eradication of cancer and in this review, we will explore two opposing approaches for modulation of Nrf2 in cancer treatments

LEKSIKOGRAFSKA IMPLEMENTACIJA INFORMACIJE O RODNOM OGRANIČENJU ILI RODNOJ PREFERENCIJI U UPOTREBI RODNO OBILJEŽENIH FRAZEMA RUSKOGA JEZIKA

The article illustrates the importance of gender-marked information as crucial pragmatic information in a lexicographical description of gender-marked idioms. Furthermore, it analyzes the existing practice of lexicographical description of Russian gender-marked idioms and suggests the possibilities of a more consistent way of implementing of this type of pragmatic information in a dictionary definition of idioms. For this purpose, the authors have conducted corpus-based research on the use of chosen idioms and an analysis of the correlation between the lexicographical description of gender-marked idioms and their appropriate use in speakers of Russian as a foreign language. The results indisputably prove a need to incorporate accurate and corpus-based data based on gender-relevant information about the use of idioms in dictionaries, as well as a need to distinguish gender usage restriction from gender usage preference when using gender-marked idioms.U radu se pokazuje važnost rodno relevantne informacije kao bitne pragmatičke informacije u leksikografskoj obradi rodno obilježenih frazema, analizira se dosadašnja praksa leksikografske obrade rodno obilježenih frazema ruskoga jezika te se predlažu mogućnosti dosljednije implementacije ovoga tipa pragmatičke informacije u rječnički opis frazema. U tu svrhu provedeno je korpusno istraživanje upotrebe odabranih frazema te ispitivanje korelacije leksikografskoga opisa rodno obilježenih frazema i njihove pravilne upotrebe kod govornika ruskoga kao stranog jezika. Rezultati neosporno dokazuju potrebu uključivanja ispravne i na korpusnim podacima utemeljene rodno relevantne informacije o upotrebi frazema u rječnike, kao i potrebu razlikovanja rodnoga ograničenja od rodne preferencije u upotrebi rodno obilježenih frazema

AQP3 and AQP5—Potential Regulators of Redox Status in Breast Cancer

Breast cancer is still one of the leading causes of mortality in the female population. Despite the campaigns for early detection, the improvement in procedures and treatment, drastic improvement in survival rate is omitted. Discovery of aquaporins, at first described as cellular plumbing system, opened new insights in processes which contribute to cancer cell motility and proliferation. As we discover new pathways activated by aquaporins, the more we realize the complexity of biological processes and the necessity to fully understand the pathways affected by specific aquaporin in order to gain the desired outcome–remission of the disease. Among the 13 human aquaporins, AQP3 and AQP5 were shown to be significantly upregulated in breast cancer indicating their role in the development of this malignancy. Therefore, these two aquaporins will be discussed for their involvement in breast cancer development, regulation of oxidative stress and redox signalling pathways leading to possibly targeting them for new therapies

The NRF2, Thioredoxin, and Glutathione System in Tumorigenesis and Anticancer Therapies

Cancer remains an elusive, highly complex disease and a global burden. Constant change by acquired mutations and metabolic reprogramming contribute to the high inter- and intratumor heterogeneity of malignant cells, their selective growth advantage, and their resistance to anticancer therapies. In the modern era of integrative biomedicine, realizing that a personalized approach could benefit therapy treatments and patients’ prognosis, we should focus on cancer-driving advantageous modifications. Namely, reactive oxygen species (ROS), known to act as regulators of cellular metabolism and growth, exhibit both negative and positive activities, as do antioxidants with potential anticancer effects. Such complexity of oxidative homeostasis is sometimes overseen in the case of studies evaluating the effects of potential anticancer antioxidants. While cancer cells often produce more ROS due to their increased growth-favoring demands, numerous conventional anticancer therapies exploit this feature to ensure selective cancer cell death triggered by excessive ROS levels, also causing serious side effects. The activation of the cellular NRF2 (nuclear factor erythroid 2 like 2) pathway and induction of cytoprotective genes accompanies an increase in ROS levels. A plethora of specific targets, including those involved in thioredoxin (TRX) and glutathione (GSH) systems, are activated by NRF2. In this paper, we briefly review preclinical research findings on the interrelated roles of the NRF2 pathway and TRX and GSH systems, with focus given to clinical findings and their relevance in carcinogenesis and anticancer treatments

Peroxiporins are induced upon oxidative stress insult and are associated with oxidative stress resistance in colon cancer cell lines

Oxidative stress can induce genetic instability and change cellular processes, resulting in colorectal cancer. Additionally, adaptation of oxidative defense causes therapy resistance, a major obstacle in successful cancer treatment. Peroxiporins are aquaporin membrane channels that facilitate H2O2 membrane permeation, crucial for regulating cell proliferation and antioxidative defense. Here, we investigated four colon cancer cell lines (Caco-2, HT-29, SW620, and HCT 116) for their sensitivity to H2O2, cellular antioxidative status, and ROS intracellular accumulation after H2O2 treatment. The expression of peroxiporins AQP1, AQP3, and AQP5 and levels of NRF2, the antioxidant transcription factor, and PPARγ, a transcription factor that regulates lipid metabolism, were evaluated before and after oxidative insult. Of the four tested cell lines, HT-29 was the most resistant and showed the highest expression of all tested peroxiporins and the lowest levels of intracellular ROS, without differences in GSH levels, catalase activity, nor NF2 and PPARγ levels. Caco-2 shows high expression of AQP3 and similar resistance as HT-29. These results imply that oxidative stress resistance can be obtained by several mechanisms other than the antioxidant defense system. Regulation of intracellular ROS through modulation of peroxiporin expression may represent an additional strategy to target the therapy resistance of cancer cells

Short overview on metabolomics approach to study pathophysiology of oxidative stress in cancer

Association of oxidative stress with carcinogenesis is well known, but not understood well, as is pathophysiology of oxidative stress generated during different types of anti-cancer treatments. Moreover, recent findings indicate that cancer associated lipid peroxidation might eventually help defending adjacent nonmalignant cells from cancer invasion. Therefore, untargeted metabolomics studies designed for advanced translational and clinical studies are needed to understand the existing paradoxes in oncology, including those related to controversial usage of antioxidants aiming to prevent or treat cancer. In this short review we have tried to put emphasis on the importance of pathophysiology of oxidative stress and lipid peroxidation in cancer development in relation to metabolic adaptation of particular types of cancer allowing us to conclude that adaptation to oxidative stress is one of the main driving forces of cancer pathophysiology. With the help of metabolomics many novel findings are being achieved thus encouraging further scientific breakthroughs. Combined with targeted qualitative and quantitative methods, especially immunochemistry, further research might reveal bio-signatures of individual patients and respective malignant diseases, leading to individualized treatment approach, according to the concepts of modern integrative medicine