Abstract:Objectives: The nuclear factor κB regulates the expression of genes involved in many processes that play a key role in the development and progression of cancer. The aim of this study was to examine the infl uence of the alpha lipoic acid in the chemoprevention of colon and cervix carcinoma in vitro. Background: In recent years, special attention has been paid to the potential chemopreventive properties of antioxidants. There are no published data on the impact of alpha lipoc acid of chemoprevention of cervix and colon cancer. Methods: We examined the effect of alpha lipoic acid alone or in combination with cisplatin and 5-fl uorouracil on proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and Caco-2 (human colon cancer cells) by MTT test. The measurement of the level of transcription factor NF-κB was also performed in the cells of both cell lines. Results: At least one of the mechanisms of the antiproliferative and/or cytotoxic effect of alpha lipoic acid on Caco-2 and HeLa cells at high concentrations, the transcription factor NF-κB, may be involved, as well as the products of transcription of genes that are under its control. Conclusion: The alpha lipoic acid has proven to be a promising candidate in the combat arena against cancer (Tab. 4, Ref. 31). Text in PDF www.elis.sk.
Abstract:In order to keep pace with the ongoing changes in ICT and increasing common IT competencies requirements, informatics curricula at secondary school level and, consequently, curricula educating informatics teachers must be frequently changed to ensure necessary competencies. This paper proposes collaborative development of informatics curricula assisted by a software tool for compatibility analysis of secondary school informatics curricula and curricula by which teachers of informatics are educated. The proposed software tool relies upon semantic technologies, i.e. ontologies for representation of competence-based curricula and ontology alignment for compatibility analysis. The secondary school informatics curriculum ontology was built to comply with the ACM K12 standard, while the teachers' curriculum ontology was built based on the selected existing curricula. The paper presents a brief description of the software tool and the results of the domain (informatics) segment of teachers' curriculum offered by the selected Serbian university and the standardized ACM K12 compliant secondary school informatics curriculum.
Summary. -In this study, a major part of genome of the pestivirus isolate 297 from Slovakia, comprising the 7195 nt-long 5΄-UTR-NS3 region was sequenced and analyzed. Conserved cleavage sites between individual viral proteins of this region were determined and the number of amino acids of respective proteins was estimated as follows: 168 for N pro , 100 for C, 227 for E rns , 195 for E1, 373 for E2, 70 for p7, 453 for NS2, and 683 for NS3. Based on sequence and phylogenetic analysis of 5΄-UTR, N pro , and E2 the isolate 297 was characterized as a border disease virus of genotype 3. It was found to be distinct from other BDV-3 strains analyzed so far, consequently forming a distinct branch within the phylogenetic clade. All these data expand a relatively limited knowledge of genetic properties of individual BDV genotypes and strains circulating in the Central Europe.Keywords: border disease virus; sheep isolate; pestivirus * Corresponding author. E-mail: vilcek@uvm.sk; phone: +421-915-984654. Abbreviations: BDV = border disease virus; BVDV-1 = bovine viral diarrhea virus 1; BVDV-2 = bovine viral diarrhea virus 2; CSFV = classical swine fever virus; 5΄-, 3΄-UTR = 5΄-, 3΄-untranslated region
Alpha-lipoic acid (ALA), a naturally-occurring antioxidant, inhibits proliferation and induces apoptosis in various cancer cell lines without effects on normal non-transformed cells. The aim of this study was to examine the effects of alpha-lipoic acid (ALA), alone and combined with 5-fluorouracil (5-FU), on Bcl-2/Bax expression in human colon cancer Caco-2 cell line as well as to investigate possible molecular mechanisms and pathways involved in ALA-mediated effects. In the present study ALA and 5-FU showed a tendency to decrease Bcl-2 and increase Bax expression. ALA exerted higher inhibitory effects on Bcl-2 expression, while the significant increase of Bax expression was shown after the treatment with the combination of ALA and 5-FU. The binding modes of ALA and 5-FU with both targets were shown to be closely similar, and some interactions the same like those of known BH3 mimetics. Thus, ALA may be considered as potential BH3 mimetic. Additionally, with in silico calculated physico-chemical properties taken into account, it was confirmed that ALA may easily be delivered to its intracellular and membrane targets. RezumatAcidul alfa-lipoic (ALA), un antioxidant natural, inhibă proliferarea și induce apoptoza la nivelul diferitelor linii celulare canceroase, fără efect asupra celulelor normale netransformate. Scopul acestui studiu a fost de a evalua efectele acidului alfalipoic (ALA), singur și combinat cu 5-fluorouracil (5-FU), asupra exprimării Bcl-2 / Bax în linia celulară Caco-2, de origine din colonul uman, ca să investigheze posibilele mecanisme moleculare și căile implicate în efectele mediate de ALA.În studiul de față ALA și 5-FU au arătat o tendință de scădere a Bcl-2 și creșterea expresiei Bax. ALA a exercitat un efect inhibitor mai mare asupra exprimării Bcl-2, în timp ce creșterea semnificativă a expresiei Bax a fost demonstrată după tratamentul combinat ALA și 5-FU. Modelele de legare a ALA și 5-FU de ambele ținte moleculare s-au dovedit a fi foarte apropiate, iar unele interacțiuni sunt identice cu cele cunoscute pentru mimeticele BH3. Astfel, ALA poate fi considerat ca potențial mimetic BH3. În plus, proprietățile fizico-chimice evaluate in silico au confirmat că ALA are un tropism deosebit pentru țintele intracelulare și membranare ale acțiunii sale.
Cyclooxygenases clearly appear to be implicated in carcinogenesis. It has been reported that COX-2 is active throughout the entire process of cancer development and progression. Various molecular mechanisms may be responsible for this. Epidemiological and experimental studies have revealed that nonselective non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors can reduce the risk of cancer. Inhibition of COX provides a plausible explanation of the data on NSAIDs and cancer. However, the molecular pathways of this effect are still unclear, more complex and likely involve multiple COX-2dependent and independent mechanisms, where pro-and anti-apoptotic Bcl-2 family members may take part. We examined the effects of ketoprofen (KT), as nonselective COX-1/2, and meloxicam (MK), as selective COX-2 inhibitor, alone and combined with 5-fluorouarcil (FU) and cisplatin (CP), on the proliferation by MTT test and Bcl-2/Bax expression in HeLa cells (human cervical carcinoma cells). MC alone or combined with conventional anticancer drugs, FU and CP, showed better cytotoxic and antiproliferative effect than KT. The levels of Bcl-2 were decreased while the levels of Bax were increased dose-dependently by KT and MC. A significant increase in the expression of Bax protein in HeLa cells was more pronounced for MC. The synergy observed in the effects of ketoprofen and meloxicam with cisplatin and 5fluorouracil on the cervical cancer cell line was generated by an enhancement of apoptosis. Therefore, ketoprofen and meloxicam may represent therapeutic candidates to improve access of cervical cancer chemoprevention and chemotherapy.
САЖЕТАККолоректални карцином је по учесталости на трећем месту међу малигним туморима особа оба пола у високо развијеним земљама. То је предоминантно болест старијих људи, и јавља се углавном после 60. године живота. Иако је етиологија карцинома колона непо-зната, претпоставља се да настаје као после-дица комплексне и недовољно разјашњене интеракције генетских фактора и чинилаца спољашње средине.Основни елемент у етиологији колоректал-ног карцинома је процес генетских промена у епителним ћелијама мукозе колона. Сматра се да специфични епидемиолошки фактори као што су стрес, хипоксија, редукован унос глу-козе и других нутрицијената, фамилијарна предиспозиција за мутагене ефекте, месо у исхрани, жучне киселине, смањен унос мине-рала и витамина као и промена пХ фецеса доводе до започињања процеса канцерогенезе у мукози дебелог црева .Хемопревенција карцинома се дефинише као употреба хемијског агенса са циљем да блокира, спречи или одложи развој или на-предак карцинома. Сматра се да је хемо-превенција једна од главних компоненти кон-троле карцинома, а многобројна истражи-вања указују на потенцијалну улогу нестеро-идних антиинфламаторних лекова у хемопре-венцији карцинома колона.Кључне речи: колоректални карцином, хемопревенција, нестероидни антиинфлама-торни лекови ABSTRACTColorectal cancer is in the third most frequent cancer among malignant tumors of both sexes in developed countries. It is predominantly a disease of older persons and occurs mostly after the age of 60. Although the etiology of colon cancer is unknown, it is assumed to arise as a result of unclear and complex interactions between genetic and environmental factors.The main element in the etiology of colorectal cancer is the process of genetic changes in epithelial cells of colon mucosa. It is believed that specific epidemiological factors such as stress, hypoxia, reduced intake of glucose and other nutrients, a hereditary predisposition to mutagenic effects, the meat in the diet, bile acids,
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