Cytotoxic stress induces transfer of mitochondria-associated human endogenous retroviral RNA and proteins between cancer cells.

About 8 % of the human genome consists of human endogenous retroviruses (HERVs), which are relicts of ancient exogenous retroviral infections incurred during evolution. Although the majority of HERVs have functional gene defects or epigenetic modifications, many of them are still able to produce retroviral proteins that have been proposed to be involved in cellular transformation and cancer development. We found that, in chemo-resistant U87RETO glioblastoma cells, cytotoxic stress induced by etoposide promotes accumulation and large-scale fission of mitochondria, associated with the detection of HERV-WE1 (syncytin-1) and HERV-FRD1 (syncytin-2) in these organelles. In addition, mitochondrial preparations also contained the corresponding receptors, i.e. ASCT2 and MFSD2. We clearly demonstrated that mitochondria associated with HERV-proteins were shuttled between adjacent cancer cells not only via tunneling tubes, but also by direct cellular uptake across the cell membrane. Furthermore, anti-syncytin-1 and anti-syncytin-2 antibodies were able to specifically block this direct cellular uptake of mitochondria even more than antibodies targeting the cognate receptors. Here, we suggest that the association of mitochondria with syncytin-1/syncytin-2 together with their respective receptors could represent a novel mechanism of cell-to-cell transfer. In chemotherapy-refractory cancer cells, this might open up attractive avenues to novel mitochondria-targeting therapies.

Management of traumatic spinal injuries in children and young adults.

PURPOSE: Spinal injuries are rarely seen in pediatric patients and therapeutic options are still poorly defined. The present study is aimed to present our experience with a rather large series of children and young adults suffering from traumatic spinal injury. PATIENTS AND METHODS: Between 1990 and 2010, 75 consecutive pediatric patients with spinal injuries were treated in our institution. Mean age was 15 years, ranging from 3 months to 21 years. Radiological findings, treatment strategies, and clinical outcome were evaluated retrospectively and compared with literature. Forty (53.3%) patients were treated conservatively and 35 patients (47%) surgically using anterior or posterior approaches. Subgroup analysis was performed depending on age groups, severity of neurological symptoms, and localization. RESULTS: Main trauma mechanisms were fall in 24 patients (38%) and motor vehicle accidents in 21 patients (28%). Complete neurological deficits were present in 17 individuals (23%) and incomplete in 36 patients (48%). Fractures were most frequently localized at the cervical region (56%) with predilection of the C 5/6 segment. Odontoid fractures were seen in 10 (13%) patients. Fractures of the lumbar and thoracic region were rare. Level of injury or clinical course did not differ between the subgroups (≤15 years versus >15 years). CONCLUSION: Nearly three fourths of all radiologically detected spinal injuries are located at the cervical spine. Complete neurological deficits after trauma was associated with a poor outcome, in particular for patients with injuries of the upper cervical spine. The use of autologous bone graft was associated with favorable long-term results and should be considered as the material of first choice for vertebral body and disc replacement.

Cervical spondylodiscitis--a clinical analysis of surgically treated patients and review of the literature.

OBJECTIVE: The aim of this study was to analyze our clinical and neurological results of surgically treated patients suffering from cervical spondylodiscitis with focusing particularly on the surgical methods used and to review the literature. PATIENTS AND METHODS: We present a series of 21 patients operated with cervical spondylodiscitis between 1998 and 2011. Basic demographic data, comorbidities, the radiological segments involved, the surgical strategy with special consideration of the material used and the clinical outcome were evaluated retrospectively. RESULTS: The mean age of 6 female and 12 male patients was 65 years (range 28-89 years). The mean follow-up was 3.7 years ranging between 4 weeks and 9 years. The leading symptom was neurological deficits rather than pain. The segments C 5/6 (n=8) and C 6/7 (n=7) were most frequently involved. Different surgical methods depending on the location, anatomical and pathological condition and extension of the lesion were performed. CONCLUSION: In conclusion, cervical spondylodiscitis could effectively be treated in the presented patient cohort by surgical decompression, debridement and PMMA or bone graft implants followed by long term antibiotic therapy. The presented surgical reconstruction technique with PMMA might be a feasible alternative to the use of bone graft or cages. The promising clinical results warrant future prospective studies to further investigate this technique.