The nature and the characteristics of bone metastases (BMs) in hepatocellular carcinoma (HCC) have not been fully explored in literature, presumably because HCC skeletal involvement was rarely diagnosed until a few years ago. Recently, the prognosis and the management of HCC clinical progression have been improved thanks to novel imaging techniques and multidisciplinary treatment approaches. As in other osteotropic cancers, both angiogenesis and the epithelial-to-mesenchymal transition play a crucial role in skeletal colonization, with the cooperation of additional factors including vascular endothelial growth factor, transforming growth factor beta, platelet-derived growth factor, insulin-like growth factors I and II, bone morphogenetic proteins, secretory protein clusterin, and others. BMs from HCC are often characterized by soft-tissue expansion with an abundant vascular component and elevated tumor burden. As the majority of metastatic bone lesions from HCC are osteolytic, they are detectable by computerized tomography only at a late stage and not usually visualized by traditional bone scintigraphy. For this reason, new imaging tools are currently being investigated, such as dual tracer positron emission computerized tomography. HCC is frequently complicated by liver failure, resulting in a lower tolerance to opioids used for pain control, but radiotherapy and other local-regional treatments are useful in the treatment of BMs from HCC.

Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early loco-regional spread and distant metastases at diagnosis, leading to dismal prognosis with a 5-year overall survival rate moderately over than 5%. This malignancy is largely resistant to chemotherapy and radiation, but the reasons of the refractoriness to the therapies is still unknown. Evidence is accumulating to indicate that the PDAC microenvironment and vascularity strongly contribute to the clinical features of this disease. In particular, PDAC is characterized by excessive dense extracellular matrix deposition associated to vasculature collapse and hypoxia with low drug delivery, explaining at least partly the low efficacy of antiangiogenic drugs in this cancer. Strategies aimed to modulate tumor stroma favoring vasculature perfusion and chemotherapeutics delivery are under investigation.

Hepatocellular carcinoma (HCC) is a cancer with a high mortality rate due to the fact that the diagnosis usually occurs at anadvanced stage. Even in case of curative surgical treatment, recurrence is common. Sorafenib and regorafenib are the only therapeutic agents that have been demonstrated to be effective in advanced HCC, thus novel curative approaches are urgently needed. Recent studies focus on the role of immune system in HCC. In fact, the unique immune response in the liver favors tolerance, which can represent a real challenge for conventional immunotherapy in these patients. Spontaneous immune responses against tumor antigens have been detected, and new immune therapies are under investigation: dendritic cell vaccination, immune-modulator strategy, and immune checkpoint inhibition. In recent years different clinical trials examining the use of immunotherapy to treat HCC have been conducted with initial promising results. This review article will summarize the literature data concerning the potential immunotherapeutic approaches in HCC patients.

Aims: Glucocorticoids are the sole drugs clinically used in Duchenne muscular dystrophy, in spite of the relevant side effects. Combination of glucocorticoids with synergistic drugs may be one strategy to lower doses and control side effects, meanwhile providing wider control of the complex pathology. This study is a preclinical evaluation of the effect of a combined treatment of amethyl-prednisolone (PDN) with taurine, a safe aminoacid with positive effects on some pathology-related events. Methods: PDN (1 mg/kg/day i.p.) and taurine (1 g/kg/day orally) were administered either alone or in combination, for 4-8 weeks to male dystrophic mdx mice chronically exercised on a treadmill. Effects were assessed in vivo and ex vivo with a variety of methodological approaches. Results: In vivo, each treatment significantly increased fore limb strength, a marked synergistic effect being observed with the combination PDN + taurine. Ex vivo, PDN + taurine completely restored the mechanical threshold, an electrophysiological index of calcium homeostasis, of extensor digitorum longus myofibres and the benefit was greater than for PDN alone. In parallel, the overactivity of voltage-independent cation channels in dystrophic myofibres was reduced. No effects were observed on plasma levels of creatine kinase, while lactate dehydrogenase was decreased by taurine and, to a minor extent, by PDN + taurine. A similar histology profile was observed in PDN and PDN + taurine-treated muscles. PDN + taurine significantly increased taurine level in fast-twitch muscle and brain, by high-pressure liquid chromatography analysis. Conclusions: The combination PDN + taurine has additive actions on in vivo and ex vivo functional end points, with less evident advantages on histopathology and biochemical markers of the disease.

Graphical abstractHighlights► An early treatment with enalapril was performed in exercised mdx mice. ► In vivo, enalapril increased mouse fore limb strength dose-dependently. ► Ex vivo, enalapril reduced muscular markers of oxidative stress and inflammation. ► Results corroborate an early role of angiotensin II in muscular dystrophy. ► Pre-clinical evidences of therapeutic interest of ACE inhibitors for therapy of DMD.