Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously developed octaarginine (R8)-modified lipid envelope-type nanoparticles for siRNA delivery (R8-MEND). Herein, we report on their ex vivo siRNA delivery to primary mouse bone marrow-derived dendritic cells (BMDCs) for potential use as a cancer vaccine. Quantitative imaging analysis of the intracellular trafficking of siRNA revealed that the dissociation process, as well as the rate of endosomal escape limits the siRNA efficiency of the prototype R8-MEND, prepared by the hydration method (R8-MEND(hydo)). Successful endosomal escape was achieved by using a pH-dependent fusogenic peptide (GALA) modified on a lipid mixture that was optimized for endosomal fusion. Furthermore, a modified protocol for the preparation of nanoparticles, mixing the siRNA/STR-R8 complex and small unilamellar vesicles (R8/GALA-MEND(SUV)), results in a more homogenous, smaller particle size, and results in a more efficient intracellular dissociation. Gene knockdown of the suppressor of cytokine signaling 1 (SOCS1), a negative-feedback regulator of the immune response in BMDCs resulted in an enhanced phosphorylation of STAT1, and the production of proinflammatory cytokines. Moreover, SOCS1-silenced BMDCs were more potent in suppressing tumor growth. Collectively, these results show that siRNA loaded in R8/GALA-MEND(SUV) efficiently suppresses endogenous gene expression and consequently enhances dendritic cell-based vaccine potency in vivo.
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PMID:Nanoparticles for ex vivo siRNA delivery to dendritic cells for cancer vaccines: programmed endosomal escape and dissociation. 2082 39

We previously developed octaarginine (R8)-modified lipid envelope-type nanoparticles for siRNA delivery (R8-MEND). Herein, we report on their ex vivo siRNA delivery to primary mouse bone marrow-derived dendritic cells (BMDCs) for potential use as a cancer vaccine. Quantitative imaging analysis of the intracellular trafficking of siRNA revealed that the dissociation process, as well as the rate of endosomal escape limits the siRNA efficiency of the prototype R8-MEND, prepared by the hydration method (R8-MEND(hydo)). Successful endosomal escape was achieved by using a pH-dependent fusogenic peptide (GALA) modified on a lipid mixture that was optimized for endosomal fusion. Furthermore, a modified protocol for the preparation of nanoparticles, mixing the siRNA/STR-R8 complex and small unilamellar vesicles (R8/GALA-MEND(SUV)), results in a more homogenous, smaller particle size, and results in a more efficient intracellular dissociation. Gene knockdown of the suppressor of cytokine signaling 1 (SOCS1), a negative-feedback regulator of the immune response in BMDCs resulted in an enhanced phosphorylation of STAT1, and the production of proinflammatory cytokines. Moreover, SOCS1-silenced BMDCs were more potent in suppressing tumor growth. Collectively, these results show that siRNA loaded in R8/GALA-MEND(SUV) efficiently suppresses endogenous gene expression and consequently enhances dendritic cell-based vaccine potency in vivo.
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PMID:Reprint of: Nanoparticles for ex vivo siRNA delivery to dendritic cells for cancer vaccines: Programmed endosomal escape and dissociation. 2008 Jan 39

Pilocytic astrocytoma (PA) is a low-grade glial tumor (WHO grade I) with predominant occurrence in pediatric patients. According to many authors, stereotactic radiosurgery (SRS) and radiotherapy (SRT) promote long-term remission or retardation of tumor progression in patients with in inoperable lesions after incomplete resection or recurrence. Therefore it is essential to determine the role of SRS and SRT in complex management of patients with deep-seated PA. Since April 2005 till May 2010 101 patient with intracranial PA was treated in department for radiation therapy of Burdenko Neurosurgical Institute. The series consisted of 70 pediatric patients (below 17 years inclusively) and 31 adults, of them--51 male and 50 female patients. Mean age was 15.1 years (9.8 years in children and 28.7 in adults). In 90 patients (89.2%) tumors were previously histologically verified (tumor resection in 83 cases and biopsy in 7). In 11 (10.8%) patients diagnosis of PA was based on clinical and neurovisualization data. In most cases SRT (66 (66.3%) patients) was preformed, the rest 35 (34.7%) patients were treated by SRS. Median follow-up from the onset of disease reached 52 months (2-228 months). Catamnestic data were available in 88 (87%) patients. By the end of catamnestic follow-up (December 2010) 87 (98.8%) patients treated by SRS and SRT were alive. Median follow-up from the start of radiation treatment was 22.7 months (6-60 months). Progression of tumor was observed in 20 patients (22.7%), in 18 of them due to cyst growth. 18 patients were reoperated. In 12 operated patients histological examination and its comparative analysis were performed. We found that alterations in the tumor tissue, accompanied by regression of solid component and progression of cystic portion, represent reactive-degenerative changes in the tumor as a consequence of radiation-induced pathomorphism. SRS and STR are effective techniques for treatment of patients with primary and recurrent PA despite regardless of localization of the tumor. There procedures should be performed shortly after non-radical resection. Control of tumor growth by the present time (median follow-up is 22.7 months) reaches 98%. "Progression" of the tumor due to enlargement of cystic portion shortly after SRT and SRS represents reactive-degenerative alterations in the tumor tissue and should not be evaluated as true recurrence; without neurological deterioration these cases do not require special treatment.
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PMID:[Stereotactic radiotherapy and radiosurgery in treatment of patients with deep-seated pilocytic astrocytomas]. 2262 49