RESUMEN
Glioblastoma (GB) is the most aggressive form of glioma and is characterized by poor prognosis and high recurrence despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB with potential diagnosis utility, we combined the analysis of The Cancer Gene Atlas and the REMBRANDT datasets plus a molecular examination of our own collection of surgical tumor resections. We determined a net reduction in the levels of the non-canonical histone H3 variant H3.3 in GB compared to lower-grade astrocytomas and oligodendrogliomas with a concomitant increase in the levels of the canonical histone H3 variants H3.1/H3.2. This increase can be potentially useful in the clinical diagnosis of high-grade gliomas, as evidenced by an immunohistochemistry screening of our cohort and can be at least partially explained by the induction of multiple histone genes encoding these canonical forms. Moreover, GBs showing low bulk levels of the H3.1/H3.2 proteins were more transcriptionally similar to low-grade gliomas than GBs showing high levels of H3.1/H3.2. In conclusion, this study identifies an imbalanced ratio between the H3 variants associated with glioma malignancy and molecular patterns relevant to the biology of gliomas, and proposes the examination of the H3.3 and H3.1/H3.2 levels to further refine diagnosis of low- and high-grade gliomas in future studies.
RESUMEN
Glioblastoma (GBM) is the most frequent and aggressive primary brain tumor and is associated with a poor prognosis. Despite the use of combined treatment approaches, recurrence is almost inevitable and survival longer than 14 or 15 months after diagnosis is low. It is therefore necessary to identify new therapeutic targets to fight GBM progression and recurrence. Some publications have pointed out the role of glioma stem cells (GSCs) as the origin of GBM. These cells, with characteristics of neural stem cells (NSC) present in physiological neurogenic niches, have been proposed as being responsible for the high resistance of GBM to current treatments such as temozolomide (TMZ). The protein Kinase C (PKC) family members play an essential role in transducing signals related with cell cycle entrance, differentiation and apoptosis in NSC and participate in distinct signaling cascades that determine NSC and GSC dynamics. Thus, PKC could be a suitable druggable target to treat recurrent GBM. Clinical trials have tested the efficacy of PKCß inhibitors, and preclinical studies have focused on other PKC isozymes. Here, we discuss the idea that other PKC isozymes may also be involved in GBM progression and that the development of a new generation of effective drugs should consider the balance between the activation of different PKC subtypes.
RESUMEN
A delay in the formation of the terminal neuroma following sciatic nerve section in rats was obtained by means of free nerve grafts sutured to the proximal stump of the sectioned sciatic nerve branches. The automutilating behaviour in these animals was statistically compared with that which follows single sciatic section and sciatic section plus end-to-end suture. The results showed that in animals with grafted nerve stumps, autotomy begins significantly later than in those with single sciatic section. However, when the self-mutilation started, it followed the same increasing evolution in both groups. These results suggest that autotomy after a nerve section is behaviour related to the aparition and nature of the terminal neuroma.
