Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe.

Glioblastoma multiforme is resistant to conventional anti-tumoral treatments due to its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis and identifying molecular targets useful on therapy. New therapeutic strategies are being tested in patients, such as Histone deacetylase inhibitors (HDACi) either alone or in combination with other therapies. Here two HDACi included in clinical trials have been tested, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), to characterize their effects on glioma cell growth in vitro and to determine the molecular changes that promote cancer cell death. We found that both HDACi reduce glioma cell viability, proliferation and clonogenicity. They have multiple effects, such as inducing the production of reactive oxygen species (ROS) and activating the mitochondrial apoptotic pathway, nevertheless cell death is not prevented by the pan-caspase inhibitor Q-VD-OPh. Importantly, we found that HDACi alter cell cycle progression by decreasing the expression of G2 checkpoint kinases Wee1 and checkpoint kinase 1 (Chk1). In addition, HDACi reduce the expression of proteins involved in DNA repair (Rad51), mitotic spindle formation (TPX2) and chromosome segregation (Survivin) in glioma cells and in human glioblastoma multiforme primary cultures. Therefore, HDACi treatment causes glioma cell entry into mitosis before DNA damage could be repaired and to the formation of an aberrant mitotic spindle that results in glioma cell death through mitotic catastrophe-induced apoptosis.

Fixed implant rehabilitation of the edentulous maxilla: clinical guidelines and case reports. Part II.

Fixed prosthetic implant reconstruction of the edentulous maxilla demands skill and state-of-the-art techniques of both the surgeon and the restorative dentist. As discussed in Part I (Implant Dent. 1999;8: 186-193), accurate diagnosis and treatment planning are essential to successful, predictable clinical results. How and where implants are placed have a lasting impact on the quality and prognosis of the final restoration. A series of clinical guidelines and considerations is reviewed with illustrative clinical treatment protocols of edentulous maxillae of unfavorable anatomy including attendant prosthetic difficulties. This article addresses the fixed implant rehabilitation of edentulous maxillas with inadequate posterior bone and favorable arch position, inadequate posterior bone and unfavorable arch position, and inadequate anterior and posterior bone and unfavorable arch position.

Fixed implant rehabilitation of the edentulous maxilla: clinical guidelines and case reports. Part I.

Fixed implant reconstruction is one of the most challenging prosthetic treatment alternatives for the edentulous maxilla. Accurate diagnosis and treatment planning are essential to successful, predictable clinical results. Decisions concerning the placement of implants may have a lasting impact on the quality and prognosis of the final restoration. A series of clinical guidelines and considerations is presented with illustrative clinical treatment protocols of edentulous maxillae that vary in degrees of anatomical and prosthetic difficulty. This article addresses the fixed implant rehabilitation of edentulous maxillas with favorable anatomy and favorable arch position, favorable anatomy, and unfavorable arch position, and unfavorable anatomy and favorable arch position.