Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs

Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors. TTFields were tested for their potential to inhibit metastatic spread of solid tumors to the lungs in two animal models: (1) Mice injected with malignant melanoma cells (B16F10) into the tail vein, (2) New Zealand White rabbits implanted with VX-2 tumors within the kidney capsule. Mice and rabbits were treated using two-directional TTFields at 100–200 kHz. Animals were either monitored for survival, or sacrificed for pathological and histological analysis of the lungs. The total number of lung surface metastases and the absolute weight of the lungs were both significantly lower in TTFields treated mice then in sham control mice. TTFields treated rabbits survived longer than sham control animals. This extension in survival was found to be due to an inhibition of metastatic spread, seeding or growth in the lungs of TTFields treated rabbits compared to controls. Histologically, extensive peri- and intra-tumoral immune cell infiltration was seen in TTFields treated rabbits only. These results raise the possibility that in addition to their proven inhibitory effect on the growth of solid tumors, TTFields may also have clinical benefit in the prevention of metastatic spread from primary tumors

Volumetric Medical Imaging Environment

We describe a graphical tool for analysis and visualization of three dimensional medical data. The application is intended to help physicians interpret the geometric structures of volumetric medical data and navigate through it easily. It combines novel approaches for segmenting the data and advanced techniques for visualizing the models which allow fast processing on a standard personal computer. The software's size and its minimal system demands make it suitable for remote operation

Recurrence of intracranial meningiomas: the role played by regional multicentricity

check; Globular single meningiomas are generally regarded as benign tumors that can be completely removed. Nevertheless, after a total macroscopic resection including the insertion zone (Grade 1 operation according to Simpson's classification), the incidence of recurrence ranged from 9% to 14% at the 5-year follow-up review. The authors have shown that single meningiomas represent only the visible predominant growth in the midst of a wide neoplastic field in the dura mater. Regional multiplicity in meningiomas would thus seem to be the rule. With this in mind, the authors propose to divide recurrences after Grade 1 operations into 1) true local and 2) false regional. A local recurrence is defined as a regrowth within the limits of the previous dural flap. Regional recurrence is when new growth develops outside the previous craniotomy site; this should not be considered as a recurrence but as a new primary site. These regional recurrences might explain some unexpected late tumor growth occurring after a Grade 1 operation. Five illustrative cases in which regional recurrence was detected by computerized tomography are presented. The authors also propose to add a supplementary grade to Simpson's surgical grading: Grade 0. This operation would entail a wide resection of the dura around the attachment zone of the meningioma. The authors hope that with a Grade 0 operation the incidence of recurrence might be reduced.</jats:p

Deficiency of HTRA2/Omi is associated with infantile neurodegeneration and 3-methylglutaconic aciduria

Background Cell survival critically depends on the integrity of mitochondria, which play a pivotal role during apoptosis. Extensive mitochondrial damage promotes release of pro-apoptotic factors from the intermembrane space of mitochondria. Released mitochondrial proteins include Smac/DIABLO and HTRA2/Omi, which inhibit the cytosolic E3 ubiquitin ligase XIAP and other inhibitors of apoptosis proteins. Aims Here we investigated the cause of extreme hypertonia at birth, alternating with hypotonia, with the subsequent appearance of extrapyramidal symptoms, lack of psychomotor development, microcephaly, intractable seizures and early death in four patients from two unrelated families. The patients showed lactic acidemia, 3-methylglutaconic aciduria, intermittent neutropenia, evolving brain atrophy and disturbed cristae structure in muscle mitochondria. Methods and results Using whole-exome sequencing, we identified missplicing mutation and a 5bp deletion in HTRA2, encoding HTRA2/Omi. This protein was completely absent from the patients' fibroblasts, whose growth was impaired and which were hypersensitive to apoptosis. Expression of HtrA2/Omi or of the proteolytically inactive HTRA2/Omi protein restored the cells' apoptotic resistance. However, cell growth was only restored by the proteolytically active protein. Conclusions This is the first report of recessive deleterious mutations in HTRA2 in human. The clinical phenotype, the increased apoptotic susceptibility and the impaired cell growth recapitulate those observed in the Htra2 knockout mice and in mutant mice with proteolytically inactive HTRA2/Omi. Together, they underscore the importance of both chaperone and proteolytic activities of HTRA2/Omi for balanced apoptosis sensitivity and for brain development. Absence of HTRA2/Omi is associated with severe neurodegenerative disorder of infancy, abnormal mitochondria, 3-methylglutaconic aciduria and increased sensitivity to apoptosis