Current Issue : July - September Volume : 2013 Issue Number : 3 Articles : 5 Articles
Malignant mesothelioma, closely linked with occupational asbestos exposure, is relatively rare in the frequency, but the patient numbers are going to increase in the next few decades all over the world. The current treatment modalities are not effective in terms of the overall survival and the quality of life. Mesothelioma mainly develops in the thoracic cavity and infrequently metastasizes to extrapleural organs. A local treatment can thereby be beneficial to the patients, and gene therapy with an intrapleural administration of vectors is one of the potential therapeutics. Preclinical studies demonstrated the efficacy of gene medicine for mesothelioma, and clinical trials with adenovirus vectors showed the safety of an intrapleural injection and a possible involvement of antitumor immune responses. Nevertheless, low transduction efficiency remains the main hurdle that hinders further clinical applications. Moreover, rapid generation of antivector antibody also inhibits transgene expressions. In this paper, we review the current status of preclinical and clinical gene therapy for malignant mesothelioma and discuss potential clinical directions of gene medicine in terms of a combinatory use with anticancer agents and with immunotherapy....
Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment\r\nmostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with\r\nchemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied.\r\nAs an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst\r\navoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease,\r\ndiscusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic\r\nintervention with nucleic acids.We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma\r\ntherapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already\r\nclinical application of nucleic acids in melanoma are discussed....
Interferon-beta (IFN-??), a well-established standard treatment for multiple sclerosis (MS), has proved to exhibit clinical efficacy.\r\nIn this study, we first evaluated the therapeutic effects for MS using human bone marrow-derived mesenchymal stem cells (hBMMSCs)\r\nas delivery vehicles with lesion-targeting capability and IFN-?? as therapeutic gene.We also engineered hBM-MSCs to secret\r\nIFN-?? (MSCs-IFN??) via adenoviral transduction and confirmed the secretory capacity of MSCs-IFN?? by an ELISA assay. MSCs-\r\nIFN??-treated mice showed inhibition of experimental autoimmune encephalomyelitis (EAE) onset, and the maximum and average\r\nscore for all animals in each group was significantly lower in the MSCs-IFN??-treated EAE mice when compared with the MSCs-\r\nGFP-treated EAE mice. Inflammatory infiltration and demyelination in the lumbar spinal cord also significantly decreased in the\r\nMSCs-IFN??-treated EAE mice compared to PBS- or MSCs-GFP-treated EAE mice. Moreover, MSCs-IFN?? treatment enhanced\r\nthe immunomodulatory effects, which suppressed proinflammatory cytokines (IFN-?? and TNF-??) and conversely increased antiinflammatory\r\ncytokines (IL-4 and IL-10). Importantly, injected MSCs-IFN?? migrated into inflamed CNS and significantly reduced\r\nfurther injury of blood-brain barrier (BBB) permeability in EAE mice.Thus, our results provide the rationale for designing novel\r\nexperimental protocols to enhance the therapeutic effects for MS using hBM-MSCs as an effective gene vehicle to deliver the\r\ntherapeutic cytokines....
Although the combination of herpes simplex virus type 1 (HSV-1) thymidine kinase (TK) with ganciclovir (GCV) has been shown\r\nas a promising suicide gene treatment strategy for glioma, the almost immunodepressive dose of GCV required for its adequate\r\nin vivo efficacy has hampered its further clinical application. Therefore, In order to reduce the GCV dose required, we aim\r\nto compare the therapeutic efficacy of HSV1-sr39TK, an HSV1-TK mutant with increased GCV prodrug catalytic activity, with\r\nwildtype TK in C6 glioma cells. Accordingly, rat C6 glioma cells were first transfected with pCDNA-TK and pCDNA-sr39TK,\r\nrespectively, and the gene transfection efficacy was verified by immunocytochemistry and western blot analysis. Then the in vivo\r\nsensitivity of these transfected C6-TK and C6-sr39TK cells to GCV was determined by 3-(4,5)-dimethylthiahiazo-(-z-y1)-3,5-diphenytetrazoliumromide\r\n(MTT) colorimetric assay and Hoechst-propidium iodide (PI) staining. Finally, a subcutaneously C6\r\nxenograft tumor model was established in the nude mice to test the in vitro efficacy of TK/GCV gene therapy. Our results showed\r\nthat, as compared with wildtype TK, HSV1-sr39TK/GCV demonstrated a stronger therapeutic efficacy against C6 glioma both in\r\nvitro and in vivo, which, by reducing the required GCV dose, might warrant its future use in the treatment of glioma under clinical\r\nsetting....
Theaimof the present study is to detect a combination method to utilize gene therapy for the treatment of Parkinson�s disease (PD).\r\nHere, a PD rat model is used for the in vivo gene therapy of a recombinant adeno-associated virus (AAV2) containing a human\r\nglutamic acid decarboxylase 65 (rAAV2-hGAD65) gene delivered to the subthalamic nucleus (STN). This is combined with the ex\r\nvivo gene delivery of tyrosine hydroxylase (TH) by fibroblasts injected into the striatum. After the treatment, the rotation behavior\r\nwas improved with the greatest efficacy in the combination group. The results of immunohistochemistry showed that hGAD65\r\ngene delivery by AAV2 successfully led to phenotypic changes of neurons in STN. And the levels of glutamic acid and GABA in\r\nthe internal segment of the globus pallidus (GPi) and substantia nigra pars reticulata (SNr) were obviously lower than the control\r\ngroups. However, hGAD65 gene transfer did not effectively protect surviving dopaminergic neurons in the SNc and VTA. This\r\nstudy suggests that subthalamic hGAD65 gene therapy and combined with TH gene therapy can alleviate symptoms of the PD\r\nmodel rats, independent of the protection the DA neurons from death....
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