Recent studies have shown that HDAC inhibitors act synergistically with camptothecin derivatives in combination therapies. To exploit this synergy, new hybrid molecules targeting simultaneously topoisomerase I and HDAC were designed. In particular, a selected multivalent agent containing a camptothecin and a SAHA-like template showed a broad spectrum of antiproliferative activity, with IC₅₀ values in the nanomolar range. Preliminary in vivo results indicated a strong antitumor activity on human mesothelioma primary cell line MM473 orthotopically xenografted in CD-1 nude mice and very high tolerability.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by the production of inflammatory factors. In order to overcome the side effects of currently used anti-inflammatory drugs, several attempts have been made to identify natural products capable of relieving RA symptoms. In this work, a herbal preparation consisting of propolis, pomegranate peel, and Aglianico grape pomace (PPP) extracts (4:1:1) was designed and evaluated for its effect on a murine collagen-induced arthritis (CIA) model. Firstly, the chemical contents of four different Italian propolis collected in the Campania region (Italy) were here reported for the first time. LC-MS analyses showed the presence of 38 constituents, identified in all propolis extracts, belonging to flavonoids and phenolic acids classes. The Pietradefusi extract was the richest one and thus was selected to design the PPP preparation for the in vivo assay. Our results highlight the impact of PPP on RA onset and progression. By using in vivo CIA models, the treatment with PPP resulted in a delayed onset of the disease and alleviated the severity of the clinical symptoms. Furthermore, we demonstrated that early PPP treatment was associated with a reduction in serum levels of IL-17, IL-1b, and IL-17–triggering cytokines.

Despite numerous clinical trials, glioblastoma (GBM) remains a tumor that is difficult to treat. The aim of this study was to investigate the potential of a new pharmacological approach, combining doxorubicin (Dox) and rapamycin (Rapa), in in vitro and in vivo GBM models. Cytotoxic and anti-proliferative effects of Rapa plus Dox treatments were analyzed in GBM cell lines. The in vivo effectiveness of these treatments was investigated in an orthotopic xenograft mice model of GBM. In vitro results demonstrated that prolonged exposure to Rapa sensitize GBM cells to Dox treatments. In vivo results demonstrated that Rapa (5 mg/kg) plus Dox (5 mg/kg) determined the major tumor growth inhibition (−97.29% vs. control) but results in greater toxicity. The combination Rapa plus Dox (2.5 mg/kg) showed a tumor inhibition like Rapa plus Dox (5 mg/kg) with a toxicity comparable to Rapa alone. Thus, this study demonstrated the efficacy of this pharmacological approach, providing the rationale for a clinical application of this combinational therapy in “poor-responder” GBM patients.