Clinical significance of epithelial-to-mesenchymal transition in laryngeal carcinoma: Its role in the different subsites

Background: During epithelial-to-mesenchymal transition, cancer cells lose adhesion capacity gaining migratory properties. The role of the process on prognosis has been evaluated in 50 cases of laryngeal carcinoma. Methods: E-cadherin, N-cadherin, β-catenin, α-catenin, γ-catenin, caveolin-1, and vimentin immunohistochemical expression were evaluated using a double score based on staining intensity and cellular localization. Results: Cytoplasmic E-cadherin and α/γ catenin staining were associated with a decrease in survival, cytoplasmic β-catenin was associated with advanced stage, and N-cadherin and vimentin expression were associated with poor differentiation and tumor relapse. On the basis of cancer cells, epithelial or mesenchymal morphological and immunophenotypic similarity we identified 4 main subgroups correlated with a transition to a more undifferentiated phenotype, which have a different pattern of relapse and survival. Conclusion: The negative prognostic role of epithelial-to-mesenchymal transition has been confirmed and a predictive role in glottic tumors has been suggested, leading us to propose epithelial-to-mesenchymal transition as an additional adverse feature in laryngeal carcinoma

A new medical record proposal to the prognostic risk assessment for mronj in oncologic patients: “Sapienza head and neck unit” proposal

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event associated with antiresorptive and antiangiogenic drugs. The use of these drugs in the treatment of cancer patients with bone metastasis is necessary and standardized in the literature. A multidisciplinary approach for the patient’s management is strongly recommended. Therefore, it should be necessary to integrate the path of these subjects with a dedicated dental screening in order to first assess the individual risk of developing a MRONJ, and then to plan dental treatments and oral hygiene sessions, and finally to schedule a follow-up to intercept and treat early osteonecrosis. The aim of this manuscript is to propose a new simple medical report to evaluate patients affected by metastatic bone cancer in order to reduce the risk of developing MRONJ

Efficacy and safety of neoadjuvant chemotherapy plus trastuzumab and pertuzumab in non-metastatic HER2-positive breast cancer in real life: NEOPEARL study.

Background In HER2+ breast cancer (BC) patients (pts) the pathological complete response (pCR) is associated with improved survival. With regimens based on the combination of trastuzumab (T), pertuzumab (P) and chemotherapy, pCR rates are slightly over 48%. We conducted a retrospective analysis on HER2+ BC pts to describe the outcomes of neoadjuvant combination of P+T and chemotherapy in the real-life setting. Methods Our cohort included 64 pts treated between Sept 2015 and Mar 2018 in 15 Italian Cancer Centers. Treatment outcomes were analyzed in terms of pCR (defined as ypT0/Tis, ypN0i-) and toxicities, recorded according to National Cancer Institute Common Toxicity Criteria. Statistical analysis was performed with T di Student test and χ2 test. Results Overall, in the 55 evaluable pts median age was 50 (range 28-77) and 29 pts (53%) were pre-menopausal. 24 pts (45%) were ER-/PgR-, 12 (21%) ER+/PgR-, 16 (29%) ER+/PgR+, median ki67 was 40. 9% of pts were cT1, 73% cT2, 13% cT3 and 5% cT4; 42 pts (76%) were cN+. All pts received 4 cycles of T (8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks) and P (loading dose 840 mg, followed by 420 mg every 3 weeks). In 42 pts T+P were administered with docetaxel (75 mg/mq every 3 weeks), in 8 pts with paclitaxel (80 mg/mq) and 5 pts received docetaxel and carboplatin (AUC5). In 13 pts also 3 cycles of anthracyclines, according to the FEC scheme, were administered. A pCR was achieved in 29 pts (53%). No significant associations were found between pCR and baseline characteristics or treatments schedule. Seven out of 55 (13%) pts reported G3-G4 toxicities (5 pts neutropenia G3-G4, 1 pt vomiting G3, 1 pt diarrhoea G3, 1 pt anemia G3). Three out of 4 pts treated with docetaxel, carboplatin and P+T reported G3/G4 toxicities. A significant association was found between chemotherapy schedule and toxicities (p = 0.004). Conclusions The association of P+T+chemotherapy improved pCR rate in HER2+ BC pts treated in the real-life setting. Our results showed that the selection of chemotherapy that will be associated with the dual blockade of HER2 is of paramount importance in order to avoid severe toxicities and increase the compliance with treatment

Review of nanomaterials in dentistry: interactions with the oral microenvironment, clinical applications, hazards, and benefits.

Interest in the use of engineered nanomaterials (ENMs) as either nanomedicines or dental materials/devices in clinical dentistry is growing. This review aims to detail the ultrafine structure, chemical composition, and reactivity of dental tissues in the context of interactions with ENMs, including the saliva, pellicle layer, and oral biofilm; then describes the applications of ENMs in dentistry in context with beneficial clinical outcomes versus potential risks. The flow rate and quality of saliva are likely to influence the behavior of ENMs in the oral cavity, but how the protein corona formed on the ENMs will alter bioavailability, or interact with the structure and proteins of the pellicle layer, as well as microbes in the biofilm, remains unclear. The tooth enamel is a dense crystalline structure that is likely to act as a barrier to ENM penetration, but underlying dentinal tubules are not. Consequently, ENMs may be used to strengthen dentine or regenerate pulp tissue. ENMs have dental applications as antibacterials for infection control, as nanofillers to improve the mechanical and bioactive properties of restoration materials, and as novel coatings on dental implants. Dentifrices and some related personal care products are already available for oral health applications. Overall, the clinical benefits generally outweigh the hazards of using ENMs in the oral cavity, and the latter should not prevent the responsible innovation of nanotechnology in dentistry. However, the clinical safety regulations for dental materials have not been specifically updated for ENMs, and some guidance on occupational health for practitioners is also needed. Knowledge gaps for future research include the formation of protein corona in the oral cavity, ENM diffusion through clinically relevant biofilms, and mechanistic investigations on how ENMs strengthen the tooth structure

A control approach for plasma density in tokamak machines

In tokamak machines, chamber pre-fill is crucial to attain plasma breakdown, while plasma density control is instrumental for several tasks such as machine protection and achievement of desired plasma performances. This paper sets the principles of a new control strategy for attaining both chamber pre-fill and plasma density regulation. Assuming that the actuation mean is a piezoelectric valve driven by a varying voltage, the proposed control laws ensure convergence to reference values of chamber pressure during pre-fill, and of plasma density during plasma discharge. Experimental results at FTU are presented to discuss weaknesses and strengths of the proposed control strategy. The whole system has been implemented by using the MARTe framework [1]. (C) 2013 Euratom-ENEA Association sulla Fusione. Published by Elsevier B.V. All rights reserved

Implant placement in oral squamous cells carcinoma patients treated with chemoradiotherapy: “Sapienza Head and Neck Unit” clinical recommendations

Abstract. – OBJECTIVE: To date, the treatment of patients affected by head and neck squamous cell carcinoma (HNSCC) is highly challenging for clinicians. Possible therapies are surgical resection of the tumor mass, radiotherapy, chemotherapy or, more often, a combined treatment that inevitably affects both normal and tumor cells. Consequently, patients’ anatomy and functions become reduced or altered. Nowadays the functional restoration is significantly improved thanks to the innovation in prosthetic rehabilitation and in radiotherapy. The current IMRT (Intensity Modulated Radiation Therapy) allows planning adequate treatments evaluating different tissues’ involvement and radiation dosage. It is possible to define the most suitable sites for implant insertion, using data provided by dose-volume histogram (DVH). This study aims to illustrate the idea of obtaining a unique CT image by blending radiation-planning CT and Cone Beam CT. PATIENTS AND METHODS: Five patients among 54 candidates were selected for this study. Selection criteria were: good general health (PS0-1), age between 18 and 72 years, absence of metastatic disease or local recurrence, disease-free interval of at least 18 months. Radiation planning CT scan and maxillo-facial CT Cone Beam of every patient were overlapped and merged. Only one CT for every evaluated patient was obtained in order to plan the most suitable areas for implant placement. RESULTS: The placement of 10 implants in 5 patients was programmed using the explained method. Patients (all male) were aged between 48 and 72 years old, with a median age of 64.4 years. In every case of this study, a modification of the initial program of implant placement was necessary. The new imaging method we are proposing was able to provide information about radiation isodoses received in the planned osseointegrated implants’ positions. CONCLUSIONS: This new method allows operators to correct their own therapy plans and choices, customizing the treatment plan on the actual condition of the patient. Moreover, it makes all the rehabilitation process safer and can reduce the risk of failure, side effects and inconveniences for the patients