Processing and properties of ultra-refractory composites based on Zr- and Hf-borides: state of the art and perspectives

High performance Ultra-High-Temperature Composites (based on zirconium and hafnium borides) are characterized by relevant and unique thermo-physical and thermo-mechanical properties, suitable for applications in Thermal Protection - Durable TPS and hot structure for reusable vehicles and in Hypersonics - Leading edges, cooled scramjet panels, struts, cowls, and nozzles. In spite of the difficult sinterability Zr- and Hf- diborides, recent results highlighted that these ceramics can be produced with full density, fine microstructure and controlled mechanical and thermal properties, through different procedures: pressureless sintering and hot pressing combined with the use of proper sintering aids, reactive synthesis/sintering procedures starting from precursors, field assisted technologies like spark plasma sintering (SPS). The selection of reinforcing phase (SiC, B4C, TaSi2, MoSi2, etc) is suitable to improve mechanical properties and oxidation resistance of ceramic composites based on ZrB2 and HfB2. Strength as high as ~ 800MPa at room temperature and up to 600 MPa at 1500?C in air were obtained, consequently to tailored compositions and processing control. SPS proved to be a very rapid fabrication process leading to refined microstructure and high properties of ultra-refractory diborides -based composite

Study of molecular mechanisms of pro-apoptotic activity of NCX 4040, a novel nitric oxide-releasing aspirin, in colon cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Despite numerous studies aimed at verifying the antitumor activity of nitric oxide-releasing nonsteroidal antiflammatory drugs (NO-NSAIDs), little is known about the molecular targets responsible for their antineoplastic properties. In the present study, we investigated the mechanisms underlying the cytotoxicity of NCX 4040, a novel NO-aspirin with promising antineoplastic action, in <it>in vitro </it>human colon cancer models.</p> <p>Methods</p> <p>The effect on tumor growth was evaluated in four human colon cancer cell lines (LoVo, LRWZ, WiDr and LoVo Dx) by sulforhodamine B assay, oxidative stress by immunohistochemistry, apoptosis by laddering assay, mitochondrial membrane potential (ΔΨ_m) by flow cytometry, and apoptosis- and chemoresistance-related markers by western-blot and real-time method, respectively. Prostaglandin E₂levels were determined by ELISA.</p> <p>Results</p> <p>NCX 4040 produced a higher cytotoxic effect in all the cell lines than that produced by other NO donors tested. In particular, in LoVo and LRWZ cells, NCX 4040 induced a cytocidal effect and apoptosis through p53 and NAG-1 expression, an early ΔΨ_mcollapse, and a sequential release of cytoplasmatic cytochrome c and caspase -9 and -3 active forms. 8-hydroxyguanine lesions, indicative of oxidative stress, were also observed. Conversely, in WiDr line, the drug caused a cytocidal effect, albeit not through apoptosis, and a concomitant increase in COX-2 activity. In LoVo Dx line, characterized by high levels drug resistance and DNA repair-related markers, only a cytostatic effect was observed, again in concomitance with the increase in COX-2 enzyme activity.</p> <p>Conclusion</p> <p>This study highlights the multiplicity of mechanisms involved in sensitivity or resistance to NCX 4040 and could provide useful indications for tailored therapy by identifying potentially drug-responsive tumors.</p

Melanoma indotto da farmaci oncologici?

Introduzione Lo sviluppo di melanoma pu\uf2 essere favorito da diversi gruppi di farmaci tra cui diuretici tiazidici, idroclorotiazide, sildenafil. In letteratura \ue8 descritta una maggiore incidenza di nuovi melanomi primari (NPM) nei pazienti oncologici trattati con inibitori BRAF e recentemente \ue8 stato riportato tale evento anche per un paziente in tripla terapia con vemurafenib, cobimetinib e atezolizumab per il melanoma metastatico. Noi presentiamo la nostra casistica di NPM nei pazienti giunti alla nostra osservazione per tossicit\ue0 cutanea in corso di trattamento oncologico. Materiali e Metodi Noi abbiamo cercato nel nostro archivio 2018-2019 quanti casi di NPM sono stati diagnosticati in 1520 pazienti giunti alla nostra osservazione per tossicit\ue0 cutanea da terapie oncologiche. Risultati In 19 mesi abbiamo diagnosticato 6 melanomi in 4 donne e 2 uomini in terapia oncologica. I melanomi si trovavano prevalentemente in zone fotoesposte: 2 tronco, 2 arto superiore, 2 viso. Il loro spessore in media \ue8 stato di 0.5mm: 1 pTis, 4 pT1a, 1 pT1b. I pazienti erano affetti da differenti tumori per i quali erano in terapia oncologica: 1 linfoma non Hodgkin B diffuso a grandi cellule, 1 melanoma, 1 carcinoide tipico polmonare, 1 adenocarcinoma polmonare, 1 carcinoma squamocellulare polmonare, 1 carcinoma mammario duttale infiltrante. Tre pazienti presentavano localizzazione primitiva al polmone ma con diversi istotipi. Tre pazienti (2F e 1 M) presentavano in anamnesi remota problematiche tiroidee: 2 carcinoma papillifero della tiroide e 1 adenoma di Plummer. Un\u2019altra paziente era stata operata anche per carcinoma mammario, carcinoma renale e leiomioma intestinale. Tutti i pazienti erano in corso di terapia oncologica: 1 lenalidomide, 1 trilogy study (vemurafeniv e cobimetinib + atezolizumab/placebo), 1 temozolide, 2 afatinib, 1 epirubicina e ciclofosfamide. Due pazienti sono deceduti. Conclusioni Il melanoma indotto da farmaci si sta rivelando essere un problema di importanza significativa. Per indagare tale fenomeno \ue8 importante spogliare completamente i pazienti in corso di visita dermatologica anche se richiesta per la sola tossicit\ue0 cutanea per effettuare un controllo nevi

Basic fibroblast growth factor and vascular endothelial growth factor serum levels in breast cancer patients and healthy women: useful as diagnostic tools?

INTRODUCTION: The aim of the present study was to analyze the relationship between the expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in breast cancer cells and the corresponding serum levels in individual patients. The study also evaluated the potential of serum levels of the two growth factors as diagnostic markers in a case–control study. METHODS: VEGF expression and bFGF expression were determined in 62 and 63 tumor samples, respectively. Serum VEGF and bFGF levels were determined in 54 and 65 healthy women and in 69 and 73 breast cancer patients, respectively, using a quantitative sandwich enzyme immunoassay technique. RESULTS: A direct correlation was observed between VEGF expression and bFGF expression in individual tumors (P = 0.001) and between serum levels (P = 0.038) in individual patients, but not between tumor cell expression and the corresponding serum level for either growth factor. Median values of serum levels in healthy women and breast cancer patients were not different for VEGF (P = 0.055), but were significantly different for bFGF (P < 0.001). The receiver operating characteristic curve identified a serum bFGF concentration of 1.0 pg/ml, with 84.9% sensitivity and 63.1% specificity, as the best cut-off value to discriminate between healthy women and breast cancer patients. An age-based subgroup analysis showed that serum values of patients older than 70 years of age mainly contributed to the high accuracy. CONCLUSIONS: Our data repropose bFGF as a noninvasive diagnostic tool for breast cancer

Usefulness of immunological detection of the human telomerase reverse transcriptase 353 histochemical detection of human telomerase catalytic component, hTERT, in human colorectal tumor and non-tumor tissue sections,

Abstract. Objective: Recent years have seen a considerable wealth of studies conducted on the potential usefulness of telomerase determination in diagnosis, prognosis and targeted cancer therapy. The frequently used Telomeric Repeat Amplification Protocol assay suffers from some drawbacks, the most important being the rate of false positives. In situ analysis using well characterised antibodies directed against the human telomerase reverse transcriptase (hTERT) would therefore appear to be important to morphologically identify the nature of telomerase positive cells. Methods: We performed immunostaining in a series of cultured cells and in normal, preneoplastic and tumour tissues from different organs using a monoclonal antibody directed against the catalytic subunit of telomerase. Results: Immunoreactivity was not observed in perennial cells of terminally differentiated cardiac and skeletal muscular tissues or in small pyramidal cells of the cerebral cortex. Conversely, it was found in other normal somatic tissues as well as in precancerous lesions and in all tumour histotypes. Conclusions: Immunohistochemistry with a well characterised hTERT-specific monoclonal antibody permitted the identification of hTERT immunopositive cells in normal somatic tissues. Whether hTERT protein detected by immunostaining with hTERT-specific Tel 3 36-10 antibody is actually the degraded form of the protein that retains hTERT antigenicity but not enzymatic function, or whether it represents the real, potentially functional catalytic subunit of the enzyme, immunohistochemistry would not seem to represent a useful tool to investigate the role of telomerase and the mechanisms involved in its regulation

Integration of reflectance confocal microscopy in sequential dermoscopy follow-up improves melanoma detection accuracy

Background Successful treatment of melanoma depends on early diagnosis, but its varied clinical presentation means that no single noninvasive method or criterion can provide reliable detection in all cases. Objectives To determine whether combining sequential dermoscopy imaging with reflectance confocal microscopy (RCM) can improve melanoma detection and reduce the burden of unnecessary excisions. Methods We conducted a retrospective study with median follow-up of 25 months. We included equivocal pigmented lesions that lacked clear dermoscopy criteria for melanoma at baseline but were excised subsequently because of changes during digital monitoring. RCM imaging was performed before excision. Main melanoma dermoscopy features, seven-point checklist score at baseline, and changes in structure and/or colour, and development of new melanoma-specific criteria at follow-up (scored as major, moderate or minor) were considered. Main melanoma RCM criteria were evaluated and diagnosis was made. Histopathological diagnosis was the reference standard for defining parameter frequency and diagnostic accuracy. Results Seventy lesions were included. Major changes were more frequently correlated with melanoma diagnosis, although one-third (four of 12) of melanomas showed moderate or minor changes. Cytological atypia and architectural disarrangement on RCM were correlated with melanoma diagnosis. A correct melanoma diagnosis was achieved with RCM in almost all cases (11 of 12, 92%). Referring for excision only those lesions with RCM-positive features and/or presenting major changes at digital dermoscopy follow-up, theoretically 27 of 58 naevi could be saved from surgery. Conclusions Integration of RCM in the clinical and instrumental strategy for managing difficult pigmented lesions provided additional diagnostic information useful in the decision-making process

Activity of Eribulin in a Primary Culture of Well-Differentiated/Dedifferentiated Adipocytic Sarcoma

Eribulin mesylate is a novel, non-taxane, synthetic microtubule inhibitor showing antitumor activity in a wide range of tumors including soft tissue sarcomas (STS). Eribulin has been recently approved for the treatment of metastatic liposarcoma (LPS) patients previously treated with anthracyclines. This work investigated the mechanism of action of this innovative antitubulin agent in well-differentiated/dedifferentiated LPS (ALT/DDLPS) which represents one of the most common adipocytic sarcoma histotypes. A primary culture of ALT/DDLPS from a 54-year-old patient was established. The anticancer activity of eribulin on the patient-derived primary culture was assessed by MTT and tunel assays. Eribulin efficacy was compared to other drugs approved for the treatment of STS. Cell migration and morphology were examined after exposure to eribulin to better understand the drug mechanism of action. Finally, Western blot analysis of apoptosis and migration proteins was performed. The results showed that eribulin exerts its antiproliferative effect by the arrest of cell motility and induction of apoptosis. Our results highlighted the activity of eribulin in the treatment of ALT/DDLPS patients