The general prevalence of the familial multi-organ tumor disorder, von Hippel-Lindau syndrome (VHL), was estimated to be 1 in 25-40,000 in western studies two decades back. Few studies were done in Indian sub-continent, amidst a surge in clinical reports on VHL specific manifestations. The syndrome is correlated with mutations of the gene VHL (located in Chr 3p25.3). We aimed to conduct a prospective case series describing phenotypic and genotypic characteristics in Indian population. The VHL-specific clinical and radiological features were collected from patients and family members. Genotypic changes such as deletion/duplication or point mutation in the VHL locus were identified using sequencing and MLPA. Thirty-one subjects, from fifteen families with diagnosed VHL, were included in the study. Multicystic pancreas was found in 71% (22/31), CNS hemangioblastoma in 68% (21/31), renal cell carcinoma and retinal angiomas in 23% (7/31) each, pheochromocytoma in 9.7% (3/31) of the population and endolymphatic sac tumor in one subject. Four families (9 subjects) had full length deletion of VHL, three families (4 subjects) had a deletion of exon 3, eight families (18 subjects) had different exonic, splice-site and intronic point mutations and one subject had a de novo in-frame indel in exon 1. Multicystic pancreas and CNS hemangioblastomas were the most common manifestations in our population. The phenotypic expression patterns in terms of tumorigenesis, tissue tropism and penetrance in comparison to the genotypic features were found to be different from previous correlative studies.
The authors report an intrinsic brainstem lesion that was diagnosed initially as a pontine cavernoma, which finally proved to be a choroid plexus papilloma. Choroid plexus papillomas are rare tumors of the central nervous system and are usually intraventricular in location. The occurrence of this tumor in an intraparenchymal location is extremely rare, and its occurrence within the brainstem is previously unreported. The authors also report a trial of chemotherapy with lomustine in the management of the residual tumor.
The combination of accurate, automated stereotaxy with image and haptic guidance can be applied to a wide range of cranial neurosurgical procedures. The facial laser scanning method offered the best registration accuracy for the ROSA system based on our retrospective analysis.
Background Nanoparticle siRNA-conjugates are promising clinical therapeutics as indicated by recent US-FDA approval. In glioma stem cells (GSC), multiple stemness associated genes were found aberrant. We report intracranially injectable, multi-gene targeted siRNA nanoparticle-gel (NPG) for the combinatorial silencing of three aberrant genes, thus inhibiting the tumorogenic potential of GSCs. Methods NPG loaded with siRNAs targeted against FAK, NOTCH-1, SOX-2 were prepared by the self-assembly of siRNAs with protamine–hyaluronic acid combination. Electron microscopy, DLS and agarose gel electrophoresis were used for the physicochemical characterisation. Cell transfection and gene-silencing efficiency were studied using human mesenchymal stem cells and rat C6 glioma derived GSCs. Neurosphere inhibition was tested in vitro using GSCs derived from C6 cell line and glioma patient samples. Patient-Derived-Xenograft model and orthotopic rat glioma model were used to test the effect of NPG on in vivo tumorigenicity. Results The siRNA nanoparticles with an average size ~ 250nm and ~ 95% loading efficiency showed cellular uptake in ~95.5% GSCs. Simultaneous gene-silencing of FAK, NOTCH-1, and SOX-2 led to the inhibition of neurosphere formation by GSCs, whereas normal stem cells remained unaffected and retained neuronal differentiation capability. GBM PDX models manifested significant impairment in the tumorigenic potential of NPG treated GSCs. Intracranial injection of NPG inhibited tumour growth in orthotopic rat brain tumour model. Conclusion Intracranially injectable n-siRNA nanoparticle-gel targeted to multiple stem-cell signalling impair glioma initiation capabilities of GSCs and inhibited tumour growth in vivo.
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