quantification-size-profiling-extracellular-vesicles-using-tunable

Quantification and Size-profiling of Extracellular Vesicles Using Tunable Resistive Pulse Sensing

Extracellular vesicles (EVs), including &#8216;microvesicles&#8217; and &#8216;exosomes&#8217;, are highly abundant in bodily fluids. Recent years have ...

University Medical Center Utrecht

Beckwith-Wiedemann syndrome (BWS) is a rare congenital syndrome characterized by gigantism, macroglossia, exophthalmos, postpartum hypoglycemia, and multiple midline defects such as omphalocele. The authors describe, to the best of their knowledge, the first case of a child in whom BWS was diagnosed and who was subsequently treated for a nasal encephalocele. Because the authors believe that this feature might not be an incidental finding in patients with BWS, intranasal masses in these patients should be carefully differentiated, as complications might be severe.

Nasal encephalocele in a child with Beckwith-Wiedemann syndrome.

Glioblastoma multiforme (GBM) is a devastating form of brain cancer for which there is no effective treatment. Here, we report a novel approach to brain tumor therapy through genetic modification of normal brain cells to block tumor growth and effect tumor regression. Previous studies have focused on the use of vector-based gene therapy for GBM by direct intratumoral injection with expression of therapeutic proteins by tumor cells themselves. However, as antitumor proteins are generally lethal to tumor cells, the therapeutic reservoir is rapidly depleted, allowing escape of residual tumor cells. Moreover, it has been difficult to achieve consistent transduction of these highly heterogeneous tumors. In our studies, we found that transduction of normal cells in the brain with an adeno-associated virus (AAV) vector encoding interferon-beta (IFN-beta) was sufficient to completely prevent tumor growth in orthotopic xenograft models of GBM, even in the contralateral hemisphere. In addition, complete eradication of established tumors was achieved through expression of IFN-beta by neurons using a neuronal-restricted promoter. To our knowledge this is the first direct demonstration of the efficacy of targeting gene delivery exclusively to normal brain cells for brain tumor therapy.

Preventing growth of brain tumors by creating a zone of resistance.

Patients with Neurofibromatosis type 1 (NF1) have an increased risk of developing neoplasms. The most common brain tumors, found in 15%-20% of NF1 patients, are hypothalamic-optic gliomas, followed by brainstem and cerebellar pilocytic astrocytomas. These tumors generally have a benign nature. NF1 patients are predisposed to a 5-fold increased incidence of high-grade astrocytomas, which are usually located in supratentorial regions of the brain. We present an NF1 patient who developed a high-grade astrocytoma in the posterior fossa and discuss possible pathophysiological mechanisms.

Glioblastoma multiforme in the posterior cranial fossa in a patient with neurofibromatosis type I.

GM1 gangliosidosis &#x662F; glycosphingolipid (GSL) &#x6EB6;&#x9176;&#x4F53;&#x8D2E;&#x79EF;&#x75C5;&#x4E73;&#x7CD6;&#x9178; &beta;-&#x82F7; (&beta;gal)&#xFF0C;&#x5176;&#x4E2D; GM1 &#x795E;&#x7ECF;&#x8282;&#x548C;&#x5176; asialo &#x5F62;&#x5F0F; &#xFF08;GA1&#xFF09; &#x4E3B;&#x8981;&#x5728;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x4E2D;&#x7684;&#x79EF;&#x7D2F;&#x4F1A;&#x5BFC;&#x81F4;&#x9057;&#x4F20;&#x7F3A;&#x9677;&#x6240;&#x81F4;&#x3002;&#x53D1;&#x75C5;&#x5E74;&#x9F84;&#x8303;&#x56F4;&#x4ECE;&#x5E7C;&#x5E74;&#x5230;&#x6210;&#x5E74;&#xFF0C;&#x548C;&#x8FC7;&#x5EA6;&#x795E;&#x7ECF;&#x8282;&#x82F7;&#x8102;&#x7D2F;&#x79EF;&#x751F;&#x4EA7;&#x9010;&#x6B65;&#x795E;&#x7ECF;&#x53D8;&#x6027;&#x548C;&#x4EBA;&#x7C7B;&#x7CBE;&#x795E;&#x8FD0;&#x52A8;&#x6027;&#x8FDF;&#x7F13;&#x3002;&#x76EE;&#x524D;&#xFF0C;&#x6CA1;&#x6709;&#x6709;&#x6548;&#x7684;&#x7597;&#x6CD5;&#xFF0C;&#x6CBB;&#x7597; GM1 gangliosidosis&#x3002;

&#x817A;&#x76F8;&#x5173;&#x75C5;&#x6BD2;&#x4ECB;&#x5BFC;&#x7684;&#x57FA;&#x56E0;&#x4F20;&#x9012;&#x6210;&#x4EBA; GM1 gangliosidosis &#x5C0F;&#x9F20;&#x7EA0;&#x6B63;&#x4E86;&#x6EB6;&#x9176;&#x4F53;&#x8D2E;&#x79EF;&#x5728;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x4E2D;&#x7684;&#xFF0C;&#x63D0;&#x9AD8;&#x4E86;&#x751F;&#x5B58;&#x3002;

GM1-gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid Î²-galactosidase (Î²gal), which results in the accumulation of GM1-ganglioside and its asialo-form (GA1) primarily in the CNS. Age of onset ranges from infancy to adulthood, and excessive ganglioside accumulation produces progressive neurodegeneration and psychomotor retardation in humans. Currently, there are no effective therapies for the treatment of GM1-gangliosidosis.

AAV-mediated gene delivery in adult GM1-gangliosidosis mice corrects lysosomal storage in CNS and improves survival.

La gangliosidose &agrave; GM1 est une maladie de surcharge lysosomale de glycosphingolipides (GSL) due &agrave; un d&eacute;ficit g&eacute;n&eacute;tique de l&#39;acide &beta;-galactosidase (&beta;gal), qui se traduit par l&#39;accumulation du ganglioside GM1 et sa asialo-forme (GA1) principalement dans le SNC. &Acirc;ge d&#39;apparition varie de la petite enfance &agrave; l&#39;&acirc;ge adulte, et accumulation du ganglioside excessif produit neurod&eacute;g&eacute;n&eacute;rescence progressive et un retard psychomoteur chez les humains. Actuellement, il n&#39;y a aucune th&eacute;rapie efficace pour le traitement de la-gangliosidose &agrave; GM1.

AAV-mediated gene livraison chez la souris adulte de gangliosidose &agrave; GM1 corrige lysosomale dans syst&egrave;me nerveux central et am&eacute;liore la survie.

GM1-Gangliosidose ist eine lysosomale Speicherkrankheit verursacht ein genetischer Mangel des sauren &Beta;Galaktosidase (&beta;gal), was die Anh&auml;ufung von GM1-Ganglioside und seiner Asialo-Form (GA1) vor allem im ZNS f&uuml;hrt Glycosphingolipide (GSL). Manifestationsalter reicht vom S&auml;uglingsalter bis zum Erwachsenenalter, und &uuml;berm&auml;&szlig;ige Ganglioside Akkumulation produziert progressive Neurodegeneration und psychomotorische Retardierung beim Menschen. Derzeit gibt es keine wirksamen Therapien f&uuml;r die Behandlung von GM1-Gangliosidose.

AAV-vermittelte gen Lieferung im Erwachsenen GM1-Gangliosidose M&auml;usen korrigiert lysosomale Speicher in CNS und &Uuml;berleben verbessert.

Gangliosidosi GM1 &egrave; una malattia da accumulo lisosomiale di glicosfingolipidi (GSL) causata da una carenza genetica di acida &beta;-galattosidasi (&beta;gal), che provoca l&#39;accumulo di gangliosidi GM1 e la sua forma asialo (GA1) principalmente nel SNC. Et&agrave; di insorgenza varia dall&#39;infanzia all&#39;et&agrave; adulta, e accumulo di gangliosidi eccessiva produce neurodegenerazione progressiva e ritardo psicomotorio nell&#39;uomo. Attualmente, non ci sono nessun terapie efficaci per il trattamento di gangliosidosi GM1.

Consegna AAV-mediata del gene in topi adulti gangliosidosi GM1 corregge lisosomiale nel sistema nervoso centrale e migliora la sopravvivenza.

GM1 &#x30AC;&#x30F3;&#x30B0;&#x30EA;&#x30AA;&#x30B7;&#x30C9;&#x30FC;&#x30B7;&#x30B9;&#x9178; &beta;-&#x30AC;&#x30E9;&#x30AF;&#x30C8;&#x30B7;&#x30C0;&#x30FC;&#x30BC; (&beta;gal) GM1 &#x30AC;&#x30F3;&#x30B0;&#x30EA;&#x30AA;&#x30B7;&#x30C9;&#x3068;&#x305D;&#x306E;&#x30A2;&#x30B7;&#x30A2;&#x30ED;-&#x30D5;&#x30A9;&#x30FC;&#x30E0; (GA1) &#x4E3B;&#x306B;&#x4E2D;&#x67A2;&#x795E;&#x7D4C;&#x7CFB;&#x306E;&#x84C4;&#x7A4D;&#x306E;&#x7D50;&#x679C;&#x306E;&#x907A;&#x4F1D;&#x7684;&#x6B20;&#x640D;&#x306B;&#x3088;&#x3063;&#x3066;&#x5F15;&#x304D;&#x8D77;&#x3053;&#x3055;&#x308C;&#x308B;&#x30B9;&#x30D5;&#x30A3;&#x30F3;&#x30B4;&#x7CD6;&#x8102;&#x8CEA; &#xFF08;&#x8102;&#x8CEA;&#xFF09; &#x30EA;&#x30BD;&#x30BD;&#x30FC;&#x30E0;&#x84C4;&#x7A4D;&#x75C7;&#x3067;&#x3059;&#x3002;&#x767A;&#x75C7;&#x5E74;&#x9F62;&#x306E;&#x5E7C;&#x5150;&#x671F;&#x304B;&#x3089;&#x6210;&#x4EBA;&#x671F;&#x306B;&#x306F;&#x3001;&#x7BC4;&#x56F2;&#x3001;&#x9032;&#x884C;&#x6027;&#x306E;&#x795E;&#x7D4C;&#x5909;&#x6027;&#x3068;&#x4EBA;&#x9593;&#x306E;&#x7CBE;&#x795E;&#x904B;&#x52D5;&#x767A;&#x9054;&#x9045;&#x6EDE;&#x30AC;&#x30F3;&#x30B0;&#x30EA;&#x30AA;&#x30B7;&#x30C9;&#x306E;&#x904E;&#x5270;&#x306A;&#x84C4;&#x7A4D;&#x3092;&#x751F;&#x6210;&#x3057;&#x307E;&#x3059;&#x3002;&#x73FE;&#x5728;&#x3001;GM1 &#x30AC;&#x30F3;&#x30B0;&#x30EA;&#x30AA;&#x30B7;&#x30C9;&#x30FC;&#x30B7;&#x30B9;&#x306E;&#x6CBB;&#x7642;&#x306E;&#x305F;&#x3081;&#x306E;&#x52B9;&#x679C;&#x7684;&#x306A;&#x6CBB;&#x7642;&#x6CD5;&#x306F;&#x3042;&#x308A;&#x307E;&#x305B;&#x3093;&#x3002;

AAV &#x5A92;&#x4ECB;&#x6027;&#x907A;&#x4F1D;&#x5B50;&#x914D;&#x4FE1;&#x5927;&#x4EBA; GM1 &#x30AC;&#x30F3;&#x30B0;&#x30EA;&#x30AA;&#x30B7;&#x30C9;&#x30FC;&#x30B7;&#x30B9; &#x30E2;&#x30C7;&#x30EB; &#x30DE;&#x30A6;&#x30B9;&#x306E;&#x4E2D;&#x67A2;&#x795E;&#x7D4C;&#x7CFB;&#x306E;&#x30E9;&#x30A4;&#x30BD;&#x30BE;&#x30FC;&#x30E0;&#x3092;&#x4FEE;&#x6B63;&#x3057;&#x3001;&#x751F;&#x5B58;&#x7387;&#x3092;&#x6539;&#x5584;&#x3057;&#x307E;&#x3059;&#x3002;

GM1 gangliosidosis &#xC0B0; &#xC131; &beta;-galactosidase&#xB97C; (&beta;gal) &#xACB0;&#xACFC; GM1 ganglioside &#xBC0F; &#xADF8;&#xAC83;&#xC758; asialo &#xD615;&#xC2DD; (GA1) CNS&#xC5D0; &#xC8FC;&#xB85C; &#xCD95;&#xC801;&#xC5D0;&#xC758; &#xC720;&#xC804;&#xC801; &#xACB0;&#xD54D;&#xC73C;&#xB85C; &#xC778; &#xD55C; glycosphingolipid (GSL) lysosomal &#xC2A4;&#xD1A0;&#xB9AC;&#xC9C0; &#xC9C8;&#xBCD1; &#xC774;&#xB2E4;. &#xBC1C;&#xBCD1; &#xB098;&#xC774; &#xBC94;&#xC704;&#xB294; &#xCD08;&#xAE30;&#xC5D0;&#xC11C; &#xC131;&#xC778; &#xAE30;, &#xADF8;&#xB9AC;&#xACE0; &#xACFC;&#xB3C4; &#xD55C; ganglioside &#xCD95;&#xC801;&#xC774; &#xC778;&#xAC04;&#xC5D0;&#xC11C; &#xC815;&#xC2E0; &#xC6B4;&#xB3D9; &#xC9C0;&#xCCB4;&#xB97C; &#xC0DD;&#xC0B0; &#xD558;&#xB294; &#xC9C4;&#xBCF4;&#xC801;&#xC778; neurodegeneration. &#xD604;&#xC7AC;, &#xAC70;&#xAE30;&#xC5D0; GM1 gangliosidosis&#xC758; &#xCE58;&#xB8CC;&#xC5D0; &#xB300; &#xD55C; &#xD6A8;&#xACFC;&#xC801;&#xC778; &#xCE58;&#xB8CC;&#xBC95; &#xC5C6;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xC131;&#xC778; GM1 gangliosidosis &#xC0DD;&#xC950;&#xC5D0;&#xC11C; AAV &#xC911;&#xC7AC; &#xC720;&#xC804;&#xC790; &#xBC30;&#xB2EC; CNS lysosomal &#xC2A4;&#xD1A0;&#xB9AC;&#xC9C0;&#xB97C; &#xC218;&#xC815; &#xD558; &#xACE0; &#xC0DD;&#xC874;&#xC744; &#xD5A5;&#xC0C1; &#xC2DC;&#xD0B5;&#xB2C8;&#xB2E4;.

Gangliosidosis gm1 es una enfermedad de almacenamiento lisosomal de glycosphingolipid (GSL) causada por una deficiencia gen&eacute;tica de la &beta;-galactosidasa &aacute;cida (&beta;gal), que da lugar a la acumulaci&oacute;n de un gangli&oacute;sido GM1 y su asialo-form (GA1) principalmente en el SNC. Edad de comienzo se extiende desde la infancia a la edad adulta, y gangli&oacute;sido excesiva acumulaci&oacute;n produce la neurodegeneraci&oacute;n progresiva y retraso psicomotor en los seres humanos. Actualmente, no hay ninguna terapias efectivas para el tratamiento de la gangliosidosis GM1.

Entrega de AAV-mediada por el gen en ratones adultos de gangliosidosis GM1 corrige almacenamiento lisosomal en SNC y mejora la supervivencia.

Many neurosurgeons remove their patients' hair before surgery. They claim that this practice reduces the chance of postoperative surgical site infections, and facilitates planning, attachment of the drapes, and closure. However, most patients dread this procedure. The authors performed the first systematic review on shaving before neurosurgical procedures to investigate whether this commonly performed procedure is based on evidence. They systematically reviewed the literature on wound infections following different shaving strategies. Data on the type of surgery, surgeryrelated infections, preoperative shaving policy, decontamination protocols, and perioperative antibiotics protocols were collected. The search detected 165 articles, of which 21 studies-involving 11,071 patients-were suitable for inclusion. Two of these studies were randomized controlled trials. The authors reviewed 13 studies that reported on the role of preoperative hair removal in craniotomies, 14 on implantation surgery, 5 on bur hole procedures, and 3 on spine surgery. Nine studies described shaving policies in pediatric patients. None of these papers provided evidence that preoperative shaving decreases the occurrence of postoperative wound infections. The authors conclude that there is no evidence to support the routine performance of preoperative hair removal in neurosurgery. Therefore, properly designed studies are needed to provide evidence for preoperative shaving recommendations.

Neurosurgery and shaving: what's the evidence?

Exosomes are a subtype of vesicles released by cells of both healthy and neoplastic origin. Preclinical studies suggest a role for tumour-derived exosomes in tumour progression, mainly through the transfer of RNA and proteins from tumour cells to other cells. The transfer of RNA and proteins by tumour-derived exosomes seems to mediate stimulation of angiogenesis and suppression of immune cells; in contrast, exosomes from healthy cells of the immune system appear to have anti-tumour characteristics. Characterisation of the RNA or protein profile of tumour-derived exosomes could have diagnostic or prognostic value, for example, in brain tumours. Anti-tumour therapies could be based on exosomes, for example, by blocking the formation of tumour-derived exosomes or having exosomes release therapeutic agents at specific sites. The most advanced application of this is the use of exosomes from dendritic cells in tumour vaccination; the safety of this has been demonstrated in phase I studies.

[Exosomes and cancer].

Cells secrete different types of membrane vesicles (MVs), which may act as important entities in normal human physiology and in various pathological processes. The established methods for quantification of MVs require purification or preanalytical handling of samples with labeling moieties.

Marike L. D. Broekman

Department of Neurosurgery,
Brain Center Rudolf Magnus

University Medical Center Utrecht

Quantification and Size-profiling of Extracellular Vesicles Using Tunable Resistive Pulse Sensing

Marike L. D. Broekman

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Neurosurgery,Brain Center Rudolf Magnus

University Medical Center Utrecht

Quantification and Size-profiling of Extracellular Vesicles Using Tunable Resistive Pulse Sensing

Department of Neurosurgery,
Brain Center Rudolf Magnus