Fatima Ardito

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

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.

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

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.

Expression of salivary biomarkers in patients with oral mucositis: evaluation by SELDI-TOF/MS

OBJECTIVE This study aims to evaluate changes in proteomic salivary profile of patients with oral mucositis after adjuvant cancer treatments. MATERIALS AND METHODS Samples were collected from patients after adjuvant cancer therapies, and were analyzed by means of SELDI/TOF. Patients were separated in two groups: patients affected by mucositis (MUCOSITIS) and patient without mucositis (NO MUCOSITIS). All patients were divided in function of the anticancer treatment: patients who had radiotherapy (MUCOSITIS RADIO), had not radiotherapy (MUCOSITIS NO RADIO), had chemotherapy (MUCOSITIS CHEMO), and those who had not chemotherapy (MUCOSITIS NO CHEMO). Statistical evaluation PCA (Principal Component Analysis) was conducted with the software BIO-RAD Data Manager(™) (Version 3.5). RESULTS We found the increased peaks of 3443, 3487, and 4135 m/z in MUCOSITIS group, while 6237 m/z was reduced. These same peaks would the same modifications in MUCOSITIS RADIO, while in MUCOSITIS CHEMIO are increased 3443 and 6237 m/z but 3487, 4135 m/z are reduced. These data were confirmed by the PCA. CONCLUSION Anticancer therapy influenced the level expression of many salivary biomarkers in mucositis with a good significance. Therefore, 3443, 3487, 4135, and 6237 m/z are good biomarker candidates of oral mucositis.

In vitro study on anti-cancer properties of genistein in tongue cancer

Purpose Tongue cancer is an extremely aggressive disease and is characterized by a poor prognosis. It is a complex disease to treat and current therapies have produced mediocre results with many side effects. Some facts suggest that natural essences can support traditional cancer therapy by carrying out a synergistic function with chemotherapy. Therefore, we evaluated the antitumor effects of genistein on tongue carcinoma cells. Methods Genistein 20, 50 and 100 µM were used for 24, 48 and 72 hours on 3 tongue carcinoma cell lines. xCELLigence system was used to evaluate the effects on cell adhesion, proliferation and to calculate IC50 values. Both MTT assay and Trypan blue assay were used to evaluate alterations in cell viability, scratch assay for cell migration and Western blot analysis for expression of some proteins. Results Cell adhesion was inhibited especially between 20 and 50 µM of genistein treatment. Proliferation was 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). Viability tests confirmed a proportional reduction in concentration of genistein and duration of treatments. Even cell migration was reduced significantly (P<0.001). Genistein down-regulates vitronectin, OCT4 and survivin. Conclusion This in vitro study clarifies the anti-tumor effect of genistein on tongue carcinoma. In vivo studies are needed to confirm these data and develop a suitable delivery system that is capable of acting directly on tumor.

Ethnicity based variation in expression of E‑cadherin in patients with squamous cell carcinoma of the oral tongue

The oral tongue is the most common site for tumours within the oral cavity. Despite intense research, there has been no improvement in the survival rate for patients with oral tongue squamous cell carcinoma (OTSCC) during the last decades. Differences between oral cancer patients based on ethno-geographical distribution have been reported. The present study used immunohistochemistry to evaluate commonly used markers of cancer cell phenotypes, E-cadherin, β-catenin and cytokeratins 5 and 19, in 120 patients with OTSCC. To evaluate the impact of ethnicity, patients from Sweden and Italy were included. A higher proportion of Swedish patients exhibited high expression of E-cadherin in their tumours (P=0.039), and high levels of E-cadherin in Swedish OTSCC patients that had succumbed to their disease were associated with poor prognosis. These data demonstrated differences in the pathological characteristics of OTSCC between two different European populations. The findings emphasise the need to take ethnicity/geographical location of patients into account when comparing results from different studies of OTSCC.

In vitro evaluation of the cytotoxic activity of three epoxy resin-based endodontic sealers

The aim of the study was to evaluate the cytotoxicity of three epoxy resin-based endodontic sealer, AH Plus, Sicura Seal and Top Seal. Direct and indirect cytotoxicity were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and LIVE/DEAD® Viability/Cytotoxicity Assay on MG63 osteoblasts-like cells. Data were statistically analyzed by analysis of variance and Tukey test, setting a significance level of 5%. Both results related to direct and indirect cell viability tests showed that all groups were significantly more cytotoxic than the negative control group. The cytotoxicity activity after one week of culture showed the absence of direct cytotoxicity, while a medium rate of indirect cytotoxicity. All the three epoxy resin-based sealers (AH Plus, Top Seal and Sicura Seal) showed a medium rate of cytotoxicity on osteoblasts-like cells in vitro. No significant difference was found among the sealers analyzed.

Genistein as a potential anticancer agent against head and neck squamous cell carcinoma

The use of nutraceuticals as protection drugs against chronic diseases gained a vast success. Many studies found that nutraceuticals may reduce the tumorigenic actions of carcinogens, inhibiting the adhesion and proliferation of tumor cells. Genistein is a natural isoflavone preventing osteoporosis, menopause problems and heart diseases. It is also known in China and Japan for its anticancer properties. The available treatment protocols for Head and neck squamous cell cancer (HNSCC) have led to poor results and new therapies are necessary. In this paper, we will review anticancer therapeutic potential of genistein and in vitro and in vivo studies that suggest its potential role in the treatments of HNSCC.

Effects of Curcumin on Squamous Cell Carcinoma of Tongue: An In Vitro Study

BACKGROUND The Squamous Cell Carcinoma of the Tongue (TSCC) is the most frequent cancer of oral cavity often characterized by poor prognosis. Conventional therapies are not very efficient and often may cause serious side effects. In this context, introduction of natural substances as possible adjuvant in the treatment and prevention of cancer is becoming a relevant topic. In fact, curcumin has been used for decades in Chinese traditional medicine for its beneficial effects. Curcumin has anticancer properties in many tumors however, its action on the tongue carcinoma is not entirely clear and many other investigations are necessary. OBJECTIVE Curcumin seems to be a good adjuvant in the treatment of head and neck tumors. However, these studies are generic and there are not many specific studies on TSCC, the most frequent and most aggressive cancer of the head-neck region. Our goal is to demonstrate its effectiveness also for TSCC. 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). The inhibition of adhesion, proliferation, viability, migration and apoptosis was studied. RESULTS IC50 value of curcumin is about 10 µM and there have been inhibitory effects even for treatments at low concentrations. Curcumin reduces migration and progression of TSCC cells and it promotes apoptosis and inhibits tumorigenesis. CONCLUSIONS These results suggest the possible use of curcumin as an anti-cancer agent in TSCC. However, in vivo studies are needed to confirm these effects and overcome its low bioavailability.

Patients with high c-MYC-expressing squamous cell carcinomas of the tongue show better survival than those with low- and medium-expressing tumours

BACKGROUND c-MYC is a potent oncoprotein with roles in a wide range of cellular processes such as differentiation, apoptosis and growth control. Deregulation of the MYC gene is commonly seen in human tumours resulting in overexpression of the protein. Here we studied expression of c-MYC in correlation to clinical outcome in patients with primary squamous cell carcinoma of the mobile tongue. METHODS Immunohistochemistry was used to identify c-MYC in a group of 104 tongue squamous cell carcinomas with an antibody directed against the N-terminal part of the protein. Staining was evaluated by multiplying the percentage of c-MYC-expressing cells with staining intensity, giving a quick score for each tumour. RESULTS All 104 tumours expressed c-MYC at varying levels. Quantitation according to per cent of positive cells and staining intensity revealed that most (15/21; 71%) high-expressing tumours were seen in males. Within the group of high c-MYC-expressing tumours, the majority were alive 2 and 5 years after treatment. CONCLUSIONS The present findings show that expression of c-MYC has prognostic value in squamous cell carcinoma of the tongue, and could be useful in choice of therapy.