In the present study, a constitutive analysis of the evolution of the mechanical response of a CrN/NbN superlattice coating exposed to high temperature has been performed. Parametric approaches were ...used to obtain a single master curve describing the experimental data as well as time-temperature-hardness maps to extrapolate the material response. Although the parametric approaches gave an excellent description of the data, an additional effort was devoted to identifying a constitutive equation similar to the power-law function widely used in creep. An excellent description was obtained for a hardness exponent close to 18 and an apparent activation energy ranging from 400 to 500kJ/mol. Possible micro-mechanisms giving reason for this value of the apparent activation energy were discussed.
Summary
Background A major problem in assessing the likelihood of survival of patients with hepatocellular carcinoma (HCC) arises from a lack of models capable of predicting outcome accurately.
Aim ...To compare the ability of the Italian score (CLIP), the French classification (GRETCH) and the Barcelona (BCLC) staging system in predicting survival in patients with HCC.
Methods We included 406 consecutive patients with cirrhosis and HCC. Seventy‐eight per cent of patients had hepatitis C. Independent predictors of survival were identified using the Cox model.
Results One‐hundred and seventy‐eight patients were treated, while 228 were untreated. The observed mortality was 60.1% in treated patients and 84.9% in untreated patients. Among treated patients, albumin, bilirubin and performance status were the only independent variables significantly associated with survival. Mortality was independently predicted by bilirubin, alpha‐fetoprotein and portal vein thrombosis in untreated patients. CLIP achieved the best discriminative capacity in the entire HCC cohort and in the advanced untreatable cases, while BCLC was the ablest in predicting survival in treated patients.
Conclusions Overall predictive ability of BCLC, CLIP and GRETCH staging systems was not satisfactory, and was not uniform for treated patients and untreated patients. None of the scoring systems provided confident prediction of survival in individual patients.
Systemic treatment for advanced hepatocellular carcinoma (HCC) has been revolutionized over the last few years following the approval of immune checkpoint inhibitors (ICI). Despite the promising ...survival extension seen with ICI combination regimens, responses are not universally seen and the optimal partner for programmed cell death 1 pathway inhibitors remains to be identified. Even fewer encouraging results have been demonstrated with ICI used for monotherapy. Several mechanisms of resistance have been described so far, involving characteristics of cancer cells (intrinsic mechanisms) and of the surrounding tumor microenvironment (extrinsic mechanisms). Factors related to therapy may also contribute to the development of resistance. Increasing research efforts are being dedicated to the discovery of novel approaches and targets to overcome resistance, some of which may be introduced into clinic in the future. Herein we describe a selection of resistance mechanisms that have been involved in impairing response to ICI and propose potential therapeutic approaches to overcome resistance.
Nanostructured Ti–B–N and Ti–Si–B–N coatings were deposited on silicon substrate by ion implantation assisted magnetron sputtering technique. To evaluate the oxidation resistance and thermal ...stability the coatings were annealed on air and in vacuum at 700–900°C. As-deposited and thermal-treated coatings were investigated by transmission electron microscope, selected area electron and x-ray diffraction, atomic force microscopy, Raman and glow discharge optical emission spectroscopy. Nanoindentaion tests were also performed. Obtained results show that Si alloying significantly improves the thermal stability of Ti–B–N coatings and increases their oxidation resistance up to 900°C. It was shown that formation of protective amorphous SiO
2
top-layer on the coating surface plays important role in the increasing of the oxidation resistance.
Despite progress in our understanding of the biology of hepatocellular carcinoma (HCC), this tumour remains difficult-to-cure for several reasons, starting from the particular disease environment ...where it arises-advanced chronic liver disease-to its heterogeneous clinical and biological behaviour. The advent, and good results, of immunotherapy for cancer called for the evaluation of its potential application also in HCC, where there is evidence of intra-hepatic immune response activation. Several studies advanced our knowledge of immune checkpoints expression in HCC, thus suggesting that immune checkpoint blockade may have a strong rationale even in the treatment of HCC. According to this background, initial studies with tremelimumab, a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor, and nivolumab, a programmed cell death protein 1 (PD-1) antibody, showed promising results, and further studies exploring the effects of other immune checkpoint inhibitors, alone or with other drugs, are currently underway. However, we are still far from the identification of the correct setting, and sequence, where these drugs might be used in clinical practice, and their actual applicability in real-life is unknown. This review focuses on HCC immunobiology and on the potential of immune checkpoint blockade therapy for this tumour, with a critical evaluation of the available trials on immune checkpoint blocking antibodies treatment for HCC. Moreover, it assesses the potential applicability of immune checkpoint inhibitors in the real-life setting, by analysing a large, multicentre cohort of Italian patients with HCC.
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