Current Issue : October - December Volume : 2012 Issue Number : 4 Articles : 6 Articles
A comparative analysis of genome-scale transcriptomic data of two types of skin cancers, melanoma and basal cell\r\ncarcinoma in comparison with other cancer types, was conducted with the aim of identifying key regulatory factors that\r\neither cause or contribute to the aggressiveness of melanoma, while basal cell carcinoma generally remains a mild disease.\r\nMultiple cancer-related pathways such as cell proliferation, apoptosis, angiogenesis, cell invasion and metastasis, are\r\nconsidered, but our focus is on energy metabolism, cell invasion and metastasis pathways. Our findings include the\r\nfollowing. (a) Both types of skin cancers use both glycolysis and increased oxidative phosphorylation (electron transfer\r\nchain) for their energy supply. (b) Advanced melanoma shows substantial up-regulation of key genes involved in fatty acid\r\nmetabolism (b-oxidation) and oxidative phosphorylation, with aerobic metabolism being far more efficient than anaerobic\r\nglycolysis, providing a source of the energetics necessary to support the rapid growth of this cancer. (c) While advanced\r\nmelanoma is similar to pancreatic cancer in terms of the activity level of genes involved in promoting cell invasion and\r\nmetastasis, the main metastatic form of basal cell carcinoma is substantially reduced in this activity, partially explaining why\r\nthis cancer type has been considered as far less aggressive. Our method of using comparative analyses of transcriptomic\r\ndata of multiple cancer types focused on specific pathways provides a novel and highly effective approach to cancer studies\r\nin general....
Motor neuron diseases (MNDs) are a rather heterogeneous group of diseases, with either sporadic or genetic origin or both, all\r\ncharacterized by the progressive degeneration of motor neurons. At the cellular level, MNDs share features such as protein misfolding\r\nand aggregation, mitochondrial damage and energy deficit, and excitotoxicity and calcium mishandling. This is particularly\r\nwell demonstrated in ALS, where both sporadic and familial forms share the same symptoms and pathological phenotype, with\r\na prominent role for mitochondrial damage and resulting oxidative stress. Based on recent data, however, altered control of gene\r\nexpression seems to be a most relevant, and previously overlooked, player in MNDs. Here we discuss which may be the links that\r\nmake pathways apparently as different as altered gene expression, mitochondrial damage, and oxidative stress converge to generate\r\na similar motoneuron-toxic phenotype....
Nonviral cationic polymers like chitosan can be combined with DNA to protect it from degradation. The chitosan is a\r\nbiocompatible, biodegradable, nontoxic, and cheap polycationic polymer with low immunogenicity. The objective of this study was\r\nto synthesize and then assess different chitosan-DNA nanoparticles and to select the best ones for selective in vitro transfection in\r\nhuman epidermoid carcinoma (KB) cell lines. It revealed that different combinations of molecular weight, the presence or absence\r\nof folic acid ligand, and different plasmid DNA sizes can lead to nanoparticles with various diameters and diverse transfection\r\nefficiencies. The intracellular trafficking, nuclear uptake, and localization are also studied by confocal microscopy, which confirmed\r\nthat DNA was delivered to cell nuclei to be expressed....
Objectives. To perform a quantitative analysis of the vascular endothelial growth factor (VEGF) gene transcription in the skin of\r\nischemic legs and provide information for VEGF in the pathogenesis in critical limb ischemia (CLI). Methods. Skin biopsies were\r\nobtained from 40 patients with CLI. Control samples came from 44 patients with chronic venous disease. VEGF gene expression\r\nwas analysed using quantitative polymerase chain reaction. Results. Patients with CLI had higher skin VEGF expression than\r\ncontrol group (RQ: 1.3 �± 0.1 versus 1, P = 0.04). Conclusions. We found an association between ischemic skin and an elevated\r\nVEGF expression in legs from patients with CLI. These data support that the mechanism for VEGF upregulation in hypoxia\r\nconditions is intact and acts appropriately in the ischaemic limbs from patients with CLI....
Current pharmacological and surgical treatments for Parkinson�s disease offer symptomatic improvements to those suffering from\r\nthis incurable degenerative neurological disorder, but none of these has convincingly shown effects on disease progression. Novel\r\napproaches based on gene therapy have several potential advantages over conventional treatment modalities. These could be used\r\nto provide more consistent dopamine supplementation, potentially providing superior symptomatic relief with fewer side effects.\r\nMore radically, gene therapy could be used to correct the imbalances in basal ganglia circuitry associated with the symptoms of\r\nParkinson�s disease, or to preserve or restore dopaminergic neurons lost during the disease process itself. The latter neuroprotective\r\napproach is the most exciting, as it could theoretically be disease modifying rather than simply symptom alleviating. Gene therapy\r\nagents using these approaches are currently making the transition from the laboratory to the bedside. This paper summarises the\r\ntheoretical approaches to gene therapy for Parkinson�s disease and the findings of clinical trials in this rapidly changing field....
Adoptive therapy with TCR gene-engineered T cells provides an attractive and feasible treatment option for cancer patients.\r\nFurther development of TCR gene therapy requires the implementation of T-cell target epitopes that prevent ââ?¬Å?on-targetââ?¬Â reactivity\r\ntowards healthy tissues and at the same time direct a clinically effective response towards tumor tissues. Candidate epitopes\r\nthat meet these criteria are MAGE-C2336-344/HLA-A2 (MC2/A2) and MAGE-A3243-258/HLA-DP4 (MA3/DP4). We molecularly\r\ncharacterized TCRaÃ?Ÿ genes of an MC2/A2-specific CD8 and MA3/DP4-specific CD4 T-cell clone derived from melanoma\r\npatients who responded clinically to MAGE vaccination.We identified MC2/A2 and MA3/DP4-specific TCR-Va3/VÃ?Ÿ28 and TCRVa38/\r\nVÃ?Ÿ2 chains and validated these TCRs in vitro upon gene transfer into primary human T cells. The MC2 and MA3 TCR were\r\nsurface-expressed and mediated CD8 T-cell functions towards melanoma cell lines and CD4 T-cell functions towards dendritic\r\ncells, respectively.We intend to start testing these MAGE-specific TCRs in phase I clinical trial....
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