Design and In Vitro Biological Evaluation of a Novel Organotin(IV) Complex with 1-(4-Carboxyphenyl)-3-ethyl-3-methylpyrrolidine-2,5-dione

A novel triphenyltin(IV) compound with 1-(4-carboxyphenyl)-3-ethyl-3-methylpyrrolidine-2,5-dione was synthesized and characterized by IR, NMR spectroscopy, mass spectrometry, and elemental analysis. In vitro anticancer activity of ligand precursor and synthesized organotin(IV) compound was determined against tumor cell lines: human adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human breast cancer (MDA-MB-453), using microculture tetrazolium test (MTT) assay. The results indicate that complex exhibited very high antiproliferative activity against all tested cell lines with IC50 values in the range of 0.22 to 0.53 mu M. The highest activity organotin(IV) compound expressed against the HeLa cells (IC50=0.22 +/- 0.04 mu M). The ligand precursor did not show anticancer activity (IC50>200 mu M). Furthermore, fluorescence microscopy analysis of HeLa cells reveal that organotin(IV) complex induced apoptosis as a mode of cell death, which is consistent with the increase of cells in the sub-G1 phase

Building a Web marketing experience: the Maltese case of Where's Everybody

L’attività di web marketing, concepita fino ad oggi come esclusiva dell’impresa, sta vivendo un’evoluzione in senso sociale e partecipativo che dipende dall’evoluzione stessa del Web. Quello che in particolare si modifica non è lo scopo, che rimane sempre la soddisfazione del cliente e la sua fidelizzazione, ma l’avere a disposizione di utilizzo una “cassetta degli strumenti” più ampia e malleabile. Partendo dalla considerazione di questo fatto, la scelta dell’argomento del presente lavoro di ricerca è avvenuta in seguito a un’esperienza lavorativa di tre mesi presso il Dipartimento di Marketing & Public Relation di Where’s Everybody, una delle maggiori aziende di produzione televisiva a Malta. Questa opportunità mi è stata offerta grazie a una borsa di studio del Progetto Leonardo. Alla luce di questa prospettiva, si è cercato innanzitutto di fornire un’accurata analisi delle variabili del macro-ambiente che rendono Malta un caso particolare in Europa, sia economico, politico che sociale e culturale. In seguito si è definito il micro-ambiente, ovvero il panorama televisivo locale e la concorrenza, con particolare attenzione alla descrizione e al target dei programmi di Where’s Everybody. Il capitolo successivo è dedicato a come il Web 2.0 sta modificando gli assi portanti dell’attività di marketing, e in generale al marketing 2.0. In particolare, saranno delineate le principali caratteristiche del web marketing, non tutte ma soltanto quelle relative al lavoro svolto e all’azienda presa in considerazione. Queste sono: lo spostamento di valore dalla transazione alla relazione; il paradigma di comunicazione many-to-many e i suoi elementi fondanti (comunità virtuale, user-generated content e passaparola); l’empowerment del consumatore e il cambiamento della definizione del marketing mix. Queste considerazioni vengono applicate nella seconda parte del lavoro, in cui vengono analizzati gli strumenti e le applicazioni di web marketing utilizzati dall’azienda maltese, prima, dopo e durante il mio periodo di lavoro. Essi sono analizzati per siti Internet, social networks e servizi streaming e on-demand. In particolare, l’analisi dei punti di forza e di debolezza dell’impiego di questi strumenti serve come spunto per presentare suggerimenti di miglioramento per la strategia complessiva, in accordo con i concetti chiave del Web 2.0, ovvero collaborazione e partecipazione degli utenti. Con ciò si dimostra che Where’s Everybody ha saputo cogliere le opportunità di evoluzione del marketing in un’ottica 2.0, comprovate dai dati forniti dall’Authority delle Comunicazioni e dalle indagini di mercato svolte dalla Media Warehouse di Malta. Lo scopo finale è quindi quello di fornire, in prima istanza, una mappatura generale dello scenario di cambiamento del Web 2.0 e conseguentemente dell’attività di marketing. In seconda istanza, preso il caso pratico di una casa di produzione televisiva non italiana, il presente lavoro si propone di offrire un esempio di azienda capace di sfruttare al meglio le effettive potenzialità dei nuovi strumenti di web marketing, sottolineando le strategie adottate e l’abilità di creare valore aggiunto per i suoi clienti

Umanjeno preživljavanje neoplastičkih humanih HeLa ćelija supstituisanim (E)-b-(benzoil) akrilnim kiselinama

The bacteriostatic activity of some of alkyl substituted (E)-β-(benzoyl)acrylic acids was shown earlier. The aim of this study was to investigate the antiproliferative action of 19 alkyl-, or halogeno-, or methoxy-, or acetamido-substituted (E)-β-(benzoyl)acrylic acids, against human cervix carcinoma, HeLa, cells. Target HeLa cells were continuously treated with increasing concentrations of substituted (E)-β-(benzoyl)acrylic acids during two days. The MTT test was used for assessment of the antiproliferative action of this group of compounds. Treatment of HeLa cells with 4-methyl-, 4-fluoro-, 4-chloro-, 4-bromo-and 4-methoxy-derivatives of (E)-β-(benzoyl) acrylic acid leads to the expression of cytostatic activity against HeLa cells (IC50 were in the range from 31-40 μM). Their antiproliferative action was less than that of the basic compound (E)-β-(benzoyl)acrylic acid whose IC50 was 28.5 μM. The 3,4-dimethyl-, 2,4-dimethyl-and 2,5-dimethyl-derivatives as well as the 4-ethyl-and 3,4-dichloro-and 2,4-dichloro-derivatives, have stronger cytostatic activity than the correspoding monosubstituted and parent compound. Their IC50 were 18.5 μM; 17.5 μM; 17.0 μM; 17.5 μM; 22.0 μM and 18 μM, respectively. The 4-iso-propyl-and 4-n-butyl-derivatives excited higher cytostatic activity than the compounds with a lower number of methylene -CH2-groups in the substitutent. Their IC50 were 14.5 μM and 6.5 μM respectively. The 2,5-di-iso-propyl-and 4-tert-butyl-derivatives expressed the most strong antiproliferative action against the investigated HeLa cells, IC50 being 4.5 μM and 5.5 μM, respectively. The investigated compounds affected the survival of HeLa cells, expressing a strong structure-activity relationship of the Hansch type.Još ranije je pokazana bakteriostatska aktivnost nekih alkil supstituisanih (E)-b-(benzoil)akrilnih kiselina. Cilj ovog rada je bio proučavanje antiproliferativnog dejstva 19 (E)-b-(benzoil)akrilnih kiselina, alkil-, ili halogeno-, ili metoksi-, ili acetamido-supstituisnaih, na ćelije humnog karcinoma grlića materice, HeLa ćelije. Ciljne HeLa ćelije, su kontinualno tretirane rastućim koncentracijama supstituisanih (E)-b-(benzoil)akrilnih kiselina tokom dva dana. MTT test je korišćen za utvrđanje antiproliferativnog dejstva ovog jedinjenja. Tretiranje HeLa ćelija 4-metil-, 4-fluoro, 4-hloro-, 4-bromo- i 4-metoksi-derivatima (E)-b-(benzoil)akrilne kiseline dovelo je do ispoljavanja citostatske aktivnosti prema HeLa ćelijama (IC50 su između 31.40 mM). Njihovo antiproliferativno dejstvo je bilo manje nego kod osnovnog jedinjenja, (E)-b-(benzoil)akrilne kiseline, čije IC50 je bilo 28,5 mM. 3,4-Dimetil-, 2,4-dimetil- i 2,5-dimetil- supstituisani, kao i 4-etil- te 3,4-dihloro-i 2,4- dihloro- derivati, imaju jaču citostatsku aktivnost od odgovarajućeg monosupstituisanog i osnovnog jedinjenja.Njihove IC50 vrednosti su 18,5 mM; 17,5 mM, 17,0 mM; 17,5 mM; 22,0 mMi18mM, u navedenom redosledu. 4-iso-Propil- i 4-n-butil-derivati pokazuju višu citostatsku aktivnost od jedinjenja sa manjim brojem metilenskih –CH2. grupa u supstituentu. Wihove IC50 vrednosti su 14,5 mM odnosno 6,5 mM. 2,5-Di-iso-propil- i 4-tert-butil- derivati ispoqavaju najjače antiproliferativno dejstvo prema ispitivanim HeLa ćelijama, IC50 su 4,5 mM i 5,5 mM u navedenom redosledu. Proučavana jedinjenja utiču na pre.ivqavawe HeLa ćelija, ispoljavajunji izrazitu relaciju Hanschovog tipa između strukture i biološke aktivnosti

Association between microRNAs 10b/21/34a and acute toxicity in glioblastoma patients treated with radiotherapy and temozolomide

A personalized approach to chemoradiation is important in reducing its potential side effects and identifying a group of patients prone to toxicity. MicroRNAs have been shown to have a predictive potential for radiotoxicity. The goal of the study was to test if levels of miRNA in peripheral blood mononuclear cells of glioblastoma patients are associated with toxicity and to identify the peak time point for toxicity. MicroRNA-10b/21/34a levels were measured in 43 patients with and without toxicity, at baseline, at the 15th, and at the 30th fraction by Real-Time quantitative Polymerase Chain Reaction. MicroRNA-10b/21 levels increased with toxicity grade (p = 0.014; p = 0.013); miR-21/34a levels were significantly different between patients with and without toxicity at the 15th fraction (p = 0.030; p = 0.045), while miR-34a levels significantly changed during treatment (p < 0.001). All three miRNAs showed a significantly high positive correlation with one another. MiR-34a might be considered as a predictive factor for toxicity due to its changes during treatment, and differences between the groups with and without toxicity; miR-10b might be used to predict toxicity; miR-10b/21 might be used for predicting the grade of toxicity in GB patients

Fucus spiralis extract and fractions: Anticancer and pharmacological potentials

Purpose: Sea macroalgae are an important source of biologically highly valuable compounds. The main aim of this study was to investigate the in vitro anticancer properties and chemical composition of the dichloromethane-methanol extract and three fractions of the Fucus spiralis from coastline of Morocco. Methods: Fractions were made from dichloromethane: methanol (1:1) extract of Fucus spiralis: petroleum-ether, ethyl-acetate and n-butanol. Extract and fractions were screened for in vitro cytotoxicity by MTT assay against human cervical adenocarcinoma (HeLa), colorectal adenocarcinoma (LS-174T), lung carcinoma (A549), and normal human lung fibroblasts (MRC-5). Cell cycle distribution of the HeLa cells was evaluated using flow cytometry. Acridine orange (AO)-ethidium bromide (EB) staining was used to assess morphological changes of HeLa cells under fluorescence microscope. Anti-migration and anti-angiogenic properties were investigated using scratch and tube formation assays against human endothelium-derived permanent EA.hy926 cell line. Antidiabetic activity was tested using anti-α-glucosidase assay. Antimicrobial effect was tested using micro- dilution method. Results: Petroleum-ether fraction оf Fucus spiralis rich in fatty acids exerted the highest cytotoxicity against HeLa cells. Ethyl-acetate and petroleum-ether fractions induced the highest accumulation of the HeLa cells in sub-G1 and G2/M phases. Extract and fractions showed proapoptotic effect on HeLa cells under fluorescent microscope. They exhibited antimigratory and antiangiogenic effects in vitro. IC50 value for α-glucosidase inhibitory activity was much stronger than standard acarbose. n-Butanol fraction exerted the highest antibacterial and antifungal activity. Conclusions: The investigation of various biological activities of the extract and fractions obtained from Fucus spiralis may suggest a promising anticancer and pharmacological potential of this edible macroalga

Antiproliferative activity of β-hydroxy- β-arylalkanoic acids

Article describes the synthesis of fifteen β-hydroxy- β-arylalkanoic acids by Reformatsky reaction using the 1-ethoxyethyl-2- bromoalkanoates, aromatic or cycloalkyl ketones or aromatic aldehydes. The short survey of previously reported synthetic procedures for title compounds, is given. The majority of obtained compounds exert antiproliferative activity in vitro toward human: HeLa, Fem-X cells, K562, and LS174 cells, having IC 50 values from 62.20 to 205 μM. The most active compound is 3-OH-2,2-di-Me-3-(4-biphenylyl)-butanoic acid, having the IC 50 value 62.20 μM toward HeLa cells. Seven examined compounds did not affect proliferation of healthy human blood peripheral mononuclear cells (PBMC and PBMC+ PHA), IC 50 > 300 μM. The preliminary QSAR results show that estimated lipophilicity of compounds influences their antiproliferative activity in the first place. The ability of dehydration, and the spatial arrangement of hydrophobic portion, HBD and HBA in molecules are has almost equal importance as lipophilicity

Supplementary data for article: Pantelić, N.; Zmejkovski, B. B.; Kolundžija, B.; Crnogorac, M. Đ.; Vujić, J. M.; Dojčinović, B.; Trifunović, S. R.; Stanojković, T. P.; Sabo, T. J.; Kaluđerović, G. N. In Vitro Antitumor Activity, Metal Uptake and Reactivity with Ascorbic Acid and BSA of Some Gold(III) Complexes with N,N′-Ethylenediamine Bidentate Ester Ligands. Journal of Inorganic Biochemistry 2017, 172, 55–66. https://doi.org/10.1016/j.jinorgbio.2017.04.001

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2017.04.001]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2478]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3070

Association of polymorphisms in TGFB1, XRCC1, XRCC3 genes and CD8 T-lymphocyte apoptosis with adverse effect of radiotherapy for prostate cancer

The genetic background of each person might affect the severity of radiotherapy (RT)-induced normal tissue toxicity. The aim of study was to evaluate the influence of TGFB1 C-509T and Leu10Pro, XRCC1 Arg280His and XRCC3 Thr241Met polymorphisms as well as the level of radiation-induced CD8 T-lymphocyte apoptosis (RILA) on adverse effects of RT for prostate cancer (PCa). The study included 88 patients with localized or locally advanced PCa who were treated with RT. The polymorphisms were determined by PCR–RFLP analysis on DNA from peripheral blood mononuclear cells. RILA values were measured by flow cytometry. We found that CT genotype of TGFB1 C-509T could be protective biomarker for acute genitourinary (GU) and gastrointestinal (GI) radiotoxicity, while Thr variant of XRCC3 Thr241Met could predict the risk for acute GU radiotoxicity. Correlation between RILA values and toxicity was not detected. Univariate logistic regression analysis showed that Gleason score and risk group were risk factors for late GU, while for late GI radiotoxicity it was diabetes mellitus type 2. However, in multivariate model those were not proven to be significant and independent risk factors. Identification of assays combination predicting individual radiosensitivity is a crucial step towards personalized RT approach

Supplementary data for article: Pantelić, N.; Zmejkovski, B. B.; Kolundžija, B.; Crnogorac, M. Đ.; Vujić, J. M.; Dojčinović, B.; Trifunović, S. R.; Stanojković, T. P.; Sabo, T. J.; Kaluđerović, G. N. In Vitro Antitumor Activity, Metal Uptake and Reactivity with Ascorbic Acid and BSA of Some Gold(III) Complexes with N,N′-Ethylenediamine Bidentate Ester Ligands. Journal of Inorganic Biochemistry 2017, 172, 55–66. https://doi.org/10.1016/j.jinorgbio.2017.04.001

Supplementary material for: [https://doi.org/10.1016/j.jinorgbio.2017.04.001]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2478]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3070

Evaluation of cytokine expression and circulating immune cell subsets as potential parameters of acute radiation toxicity in prostate cancer patients

One of the challenges of radiation oncology in the era of personalized medicine is identification of biomarkers associated with individual radiosensitivity. The aim of research was to evaluate the possible clinical value of the associations between clinical, physical, and biological factors, and risk for development of acute radiotoxicity in patients with prostate cancer. The study involved forty four patients treated with three-dimensional conformal radiotherapy. The concentrations of IL-1β, IL-2, IL-6, IFN-γ and TGF-β1 were assessed before radiotherapy, after 5th, 15th and 25th radiotherapy fractions, at the end, and 1 month after the end of radiotherapy. Cytokine gene expression was determined in peripheral blood mononuclear cells. The univariate analysis of circulating cytokine levels during radiotherapy showed that increased serum concentrations of IL-6 were significantly associated with higher grade of acute genitourinary toxicity. The multivariate analysis demonstrated that increased level of IL-6 during the radiotherapy was significantly associated with higher grade of acute genitourinary toxicity across treatment. TGF-β expression levels significantly decreased during course of radiotherapy. Research indicates that changes in circulating cytokine levels might be important parameter of radiotoxicity in patients with prostate cancer. These findings suggest that future studies based on multi-parameter examination are necessary for prediction of individual radiosensitivity