Vacuolar Proton-Translocating ATPase May Take Part in the Drug Resistance Phenotype of Glioma Stem Cells.

The vacuolar proton-translocating ATPase (V-ATPase) is a transmembrane multi-protein complex fundamental in maintaining a normal intracellular pH. In the tumoral contest, its role is crucial since the metabolism underlying carcinogenesis is mainly based on anaerobic glycolytic reactions. Moreover, neoplastic cells use the V-ATPase to extrude chemotherapy drugs into the extra-cellular compartment as a drug resistance mechanism. In glioblastoma (GBM), the most malignant and incurable primary brain tumor, the expression of this pump is upregulated, making it a new possible therapeutic target. In this work, the bafilomycin A1-induced inhibition of V-ATPase in patient-derived glioma stem cell (GSC) lines was evaluated together with temozolomide, the first-line therapy against GBM. In contrast with previous published data, the proposed treatment did not overcome resistance to the standard therapy. In addition, our data showed that nanomolar dosages of bafilomycin A1 led to the blockage of the autophagy process and cellular necrosis, making the drug unusable in models which are more complex. Nevertheless, the increased expression of V-ATPase following bafilomycin A1 suggests a critical role of the proton pump in GBM stem components, encouraging the search for novel strategies to limit its activity in order to circumvent resistance to conventional therapy.

Is Gender a Factor Affecting Long-Term Heterotopic Ossification Incidence After Single-Level Cervical Disc Arthroplasty?

BACKGROUND: Cervical disc diseases have been treated by cervical disc arthroplasty (CDA). Nevertheless, some patients will experience a mobility failure in their cervical prostheses over time because of heterotopic ossification. The aim of this study was to investigate the role of gender in long-term outcomes after CDA. METHODS: A retrospective, single-center study of patients who underwent single-level CDA with a BRYAN Cervical Disc prosthesis was performed, including a narrative review about gender differences in both structural and biomechanical features of the cervical spine. RESULTS: Study patients (14 men, 30 women) had an average follow-up of 9.8 ± 3.2 years. Significant differences emerged between genders for specific items in Neck Disability Index preoperative evaluation, with women reporting worse pain scores (P = 0.05). After stratification by age, we found a higher preoperative overall Neck Disability Index score for female patients <36 years of age (P = 0.03). In an intergender, body mass index-specific comparison, we also found a significant difference in Neck Disability Index preoperative score with normal-weight male patients faring worse than overweight male patients (P = 0.05). At a radiological level, we found a tendency toward a higher heterotopic ossification incidence in male patients (62% in men, 17% in women, P = 0.06). The female cervical spine has distinctive features, including bone structure, muscular action, soft tissue response, and genetic and epigenetic response to osteoarthritis. CONCLUSIONS: The incidence of mobility failure in our series of single-level CDA was lower in female patients. Several gender-specific factors both in static and in dynamic features may play a significant role in spinal pathology and CDA long-term radiological outcome.