1,720,972 research outputs found

    In vitro study on anticancer properties of Curcumin and Genistein in Squamous Cell Carcinoma of Tongue

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    Introduzione: Il carcinoma a cellule squamose della lingua (TSCC) è il più frequente tumore della cavità orale ed è estremamente aggressivo e caratterizzato da prognosi infausta. Si tratta di una malattia complessa da curare e le terapie in uso hanno portato a risultati mediocri e molti effetti collaterali. Alcune evidente scientifiche suggeriscono che le sostanze naturali sono in grado di supportare la terapia del cancro tradizionale, svolgendo una funzione sinergica con la chemioterapia In particolare, la curcumina è usata da decenni nella medicina cinese per i suoi effetti benefici, mentre la genisteina è un isoflavone che è conosciuto come un inibitore dell'angiogenesi e dei fitoestrogeni Curcumina e genisteina hanno proprietà antitumorali per molti tumori ma la loro azione sul carcinoma della lingua non è del tutto chiaro e sono necessarie molte altre indagini. Materiali e metodi: In questo studio, abbiamo valutato gli effetti della curcumina sulle cellule di TSCC utilizzando diverse concentrazioni (1, 5, 10, 20 e 50 μM) e 3 differenti tempi di trattamento (24, 48 e 72 ore). Inoltre, 20, 50 e 100 μM di genisteina sono utilizzati per gli stessi time points. Sono stati studiati l’inibizione di adesione, proliferazione, vitalità, migrazione e tumorigenesi. L’xCELLigence system è stato utilizzato per valutare gli effetti sull’ adesione cellulare, la proliferazione e per calcolare i valori di IC50. L’ MTT assay e il trypan blu sono stati usati per valutare la vitalità cellulare, lo scratch assay per migrazione cellulare e il western blot per l'espressione di alcune proteine. Sono stati usati per determinare possibili cambiamenti biochimici e strutturali responsabili danno cellulare: Kit per la detenzione del calcio, per la quantizzazione dell’ATP, il kit per LDH, la quantificazione del livello intracellulare dei ROS, l’analisi del ΔΨm mediante fluorescenza. Risultati: Abbiamo monitorato in tempo reale la cinetica di crescita per 72 ore dopo i trattamenti e tutti i valori CI sono stati analizzati. L'intervallo di adesione era compreso tra 0-10 ore. Abbiamo trovato una dimensione dell'adesione cellulare dopo il trattamento con 5 μM di curcumina, una riduzione di ~ 25% dopo il trattamento con 1 μM di curcumina. Inoltre, l'adesione di cellule TSCC trattate con 50 μM di curcumina è stata ridotta del 75% rispetto al controllo. Anche la riduzione della espressione dell'integrina supporta la teoria che la curcumina inibisce l'adesione delle cellule tumorali della lingua. Mentre, la curcumina riduce la proliferazione del 50% dopo trattamento con 5-10μM curcumina a tutti i time points considerati e il valore di IC50 è ~ 10 μM. La curcumina riduce la vitalità, la migrazione e la progressione delle cellule di TSCC. Inoltre, essa promuove l'apoptosi e inibisce tumorigenesi. Infatti, PAR-4 aumenta dopo trattamenti con curcumina mentre Survivina e Oct4 diminuiscono Mentre, l’adesione cellulare delle cellule TSCC viene inibita in particolare tra 20 e 50 μM di trattamento genisteina. La proliferazione è ridotta del 50% per i trattamenti con 20 μM a 24 ore, con 20 -50 μM a 48 ore e 50 μM a 72 ore (p <0,0001). I test di vitalità hanno confermato una riduzione proporzionale alla concentrazione di genisteina, aumentando proporzionalmente con il passare del tempo. Anche la migrazione sembra essere ridotta con elevata significatività (p <0.001). La genisteina sottoregolata l’espressione di vitronectina, Oct4 e survivina. È stato dimostrato un aumento del rilascio intracellulare Ca2+ e LDH mentre c'è stata una riduzione dei livelli di ATP dopo trattamenti di curcumina e genisteina. Inoltre, ROS e ΔΨm sono stati ridotti dopo i trattamenti. Tali modificazioni biochimiche hanno confermato il danno cellulare e induzione dell’apoptosi dopo i trattamenti. Conclusioni: Questi risultati suggeriscono il possibile uso di curcumina e genisteina come agenti antitumorali per terapie del TSCC. Studi in vivo sono necessari per confermare questi dati e per poter produrre un sistema di delivery in grado di agire direttamente nel sito del tumore.Background: The squamous cell carcinoma of the tongue (TSCC) is the most frequent cancer of oral cavity and is extremely aggressive and characterized by poor prognosis. It is a complex disease to be treated and therapies in use have led to mediocre results and many side effects. Some facts suggest that natural essences can support traditional cancer therapy, carrying out a synergistic function with chemotherapy In particular, curcumin is used for decades in Chinese medicine for its beneficial effects, while genistein is an isoflavone that is known as an angiogenesis inhibitor and a phytoestrogen Curcumin and genistein have anticancer properties in many tumors but their action on the tongue carcinoma is not entirely clear and many other investigations are necessary. Methods: In this study, we evaluated the effects of curcumin on TSCC cells using different concentrations (1, 5, 10, 20 and 50 μM) and 3 different treatment times (24, 48 and 72 hours). Furthermore, 20, 50 and 100 μM of genistein are used at the same time points. The inhibition of adhesion, proliferation, viability, migration and tumorigenesis were studied. Calcium Colorimetric Assay Kit, ATP-measurement methods, LDH Cytotoxicity Assay, quantitative determination of intracellular ROS level, analysis of ΔΨm by fluorescence assay were used to determinate biochemical changes responsible for cellular injury. Results: We monitored in real time the growth kinetics for 72 hours after treatment and all CI values analyzed. The adhesion interval was 0-10 hours. We found a halving of cell adhesion after treatment with 5 μM of curcumin, a ~ 25% reduction after treatment with 1 μM of curcumin. Furthermore, adhesion of TSCC cells treated with 50 μM of curcumin was reduced by 75% compared to control. Even, the down-regulation of integrin expression supports the theory goes that curcumin inhibits adhesion of the tongue cancer cells. The proliferation is reduced by 50% after treatment with 5-10μM curcumin at all time points considered and IC50 value is ~ 10 μM. Curcumin reduces vitality, migration and progression of TSCC cells and it promotes apoptosis and inhibits tumorigenesis. In fact, PAR 4 is increased after curcumin treatments while Survivin and Oct4 decreased. While, cell adhesion of TSCC cells is inhibited especially between 20 and 50 μM of genistein treatment. Proliferation is reduced by 50% for treatments with 20 μM at 24 hours, with 20 or 50 μM at 48 and 50 μM at 72 hours (p <0.0001). The viability and migration appeared to be reduced with high significance (p <0.001). Genistein downregulated vitronectin, oct4 and survivin. It was showed an increase of intracellular Ca2+ and LDH release while there was a reduction of ATP levels after treatments of curcumin and genistein. Also ROS and ΔΨm were reduced after treatments. These biochemical changes have confirmed the cell damage and consequently apoptosis after treatments. Conclusions: These results suggest the possible use of curcumin and genistein as anticancer agents in TSCC. In vivo studies are needed to confirm these data and to be able to manufacture a suitable delivery system that is acting directly in the tumor site

    The crucial role of protein phosphorylation in cell signaling and its use as targeted therapy (Review)

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    Abstract. Protein phosphorylation is an important cellular regulatory mechanism as many enzymes and receptors are activated/deactivated by phosphorylation and dephosphorylation events, by means of kinases and phosphatases. In particular, the protein kinases are responsible for cellular transduction signaling and their hyperactivity, malfunction or overexpression can be found in several diseases, mostly tumors. Therefore, it is evident that the use of kinase inhibitors can be valuable for the treatment of cancer. In this review, we discuss the mechanism of action of phosphorylation, with particular attention to the importance of phosphorylation under physiological and pathological conditions. We also discuss the possibility of using kinase inhibitors in the treatment of tumors

    Circulating miRNAs from blood, plasma or serum as promising clinical biomarkers in oral squamous cell carcinoma: A systematic review of current findings

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    The purpose of this systematic review was to summarize current findings on the use of circulating miRNAs from blood, serum and plasma as cancer biomarkers in patients with oral squamous cell carcinoma. Studies were gathered after searching four different electronic databases: PUBMED, SCOPUS, Cochrane Library and Web of Science. Additional search was carried out through cross check on bibliography of selected articles. After the selection process made by two of the authors, 16 articles met the inclusion criteria and were included in the review. Results showed that circulating miRNAs from blood, serum or plasma represent promising candidates as cancer biomarkers in patients suffering from oral cancer. The possibility to predict recurrences and metastases through follow-up quantification of candidate miRNAs represents another potential feature to be addressed in future studies. However, methodological standardization and uniform sampling is needed to increase the power and accuracy of results

    Oral mucositis: a survey on changes in the proteomic profile

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    Objectives. Oral mucositis is the most severe complication of anticancer therapy. It occurs in 40-85% of patients during chemotherapy and radiotherapy but also in patients who have undergone hematopoietic stem cell transplantation. The symptoms for oral mucositis are burning and severe pain oral, spontaneous bleeding, dysphagia, dysarthria and odynophagia; especially pain and burning sensation on swallowing contribute to decreased quality of life for oncologic patients and, in severe cases, may also force the patient to feed parenterally (1). Furthermore, if the mucositis is severe it can lead to partial or complete interruption of radiotherapy before completion of the treatment protocol with consequent worsening of the prognosis (2, 3). Dentists must be familiar with the necessary intervents, in order to help the patient during the course of the treatment and prevent the interruption. Certain measures may help minimize the symptoms associated with oral mucositis; however, further research is required, focusing on lesion prevention prior to treatment initiation. To this end, it has been investigated the salivary proteome of cancer patients who developed oral mucositis, post chemotherapy and/or radiotherapy. In addition, we compared the salivary proteome of the same subjects before developing oral mucositis and immediately after the treatment for the mucositis. The analysis was made with SELDI technology. Methods. In the current study, 55 saliva samples of patients suffering from different types of cancer were analyzed. The saliva was collected in three times: before the development of mucositis, when it was diagnosed and after the resolution of this pathology. All samples were analyzed by SELDI-TOF/MS analysis. It was possible to create cluster peaks in spectra obtained using BIORAD DataManagerTM software (Ver 3.5). Results. From this analysis we identified a list of differently expressed mass peaks (clusters). We have selected some significant peaks in a range of values between 3000 m/z 15000 m/z. In particular, five were found to be differentially expressed: 3343, 3486, 3732, 4132 and 4786 m/z. The analysis of the cluster, we evaluated different patterns of peaks in the three groups; some of these were up regulated, as the peak 3732 m/z in samples pre mucositis, and down regulated, such as the 7101 m/z in the samples pre mucositis. It is noted, moreover, an important increase of the peak 4132 m/z in samples of mucositis. Conclusions. Oral mucositis is one of the most frequent complications of cancer therapies. It is, therefore, extremely important that the mucositis is prevented whenever possible, or at least treated to reduce its severity and possible complications. Knowing the salivary proteome and its variations in a state of pre mucositis, mucositis and post mucositis can be useful in order to intervene with preventive tools and better therapies. The association of the peaks 3343, 3486, 3732, 4132 and 4786 m / z, in particular the increase in expression of the peak 4132 m / z in samples of mucositis makes us think that it can be used as biomarker of this condition. Therefore, if these data will be confirmed on a larger series of patients could identify these proteins and study of targeted therapies. Furthermore, it would be helpful to understand whether these variations are associated with a particular chemotherapy and evaluate longer available cancer therapies replacement

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Evaluation of chemical-physical properties and cytocompatibility of TheraCal LC

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    TheraCal LC (TLC, Bisco Inc., Schaumburg, IL, USA) is a light-cured, resin-modified, calcium silicate-filled base/liner material designed for direct and indirect pulp-capping. In this study the result of the evaluation in vitro of the biocompatibility and chemical-physical properties of TLC are reported. TLC specimens were prepared under aseptic conditions in strict compliance with the manufacturers instructions and sterilized. Osteoblast-like cells (MG63) were used. For different time points, solubility, water uptake, alkalinizing activity and cytotoxicity were evaluated. In ddH20 and in DMEM+FBS, TLC showed a loss of material increasing simultaneously with the absorption capacity. The increase of water uptake of the material promoting the solubilization of mineral ions in medium is a requisite for a bioactive material. The alkalinizing activity is correlated to antimicrobial/bacteriostatic activity and to the ability to favor the formation of apatite deposits. The pH values for water absorption after immersion of the disks ranged between 8 and 9 at each times of evaluation. Cytotoxicity was not observed in MG63 cells treated with TLC and after 5 days, the cells were organized to form a confluent monolayer as demonstrated by fluorescence microscopy observation. TLC showed biocompatibility on MG63 cells allowing a physiologic cell growth and differentiation. The chemical-physical properties and biocompatibility of TLC observed in vitro in the present study, allows considering this cement as an innovative pulp-capping material for the vital pulp therapy
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