| 1. |
- Stanton, Biba R, et al.
(författare)
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Diffusion tensor imaging in sporadic and familial (D90A SOD1) forms of amyotrophic lateral sclerosis
- 2009
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Ingår i: Archives of Neurology. - : American Medical Association. - 0003-9942 .- 1538-3687. ; 66:1, s. 109-115
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The basis of heterogeneity in the clinical presentation and rate of progression of amyotrophic lateral sclerosis (ALS) is poorly understood. OBJECTIVES: To use diffusion tensor imaging as a measure of axonal pathologic features in vivo in ALS and to compare a homogeneous form of familial ALS (homozygous D90A SOD1 [superoxide dismutase 1]) with sporadic ALS. DESIGN: Cross-sectional diffusion tensor imaging study. SETTING: Tertiary referral neurology clinic. PATIENTS: Twenty patients with sporadic ALS, 6 patients with homozygous D90A SOD1 ALS, and 21 healthy control subjects. MAIN OUTCOME MEASURE: Fractional anisotropy in cerebral white matter. RESULTS: Patients with homozygous D90A SOD1 ALS showed less extensive pathologic white matter in motor and extramotor pathways compared with patients with sporadic ALS, despite similar disease severity assessed clinically using a standard functional rating scale. Fractional anisotropy correlated with clinical measures of severity and upper motor neuron involvement. CONCLUSION: In vivo diffusion tensor imaging measures demonstrate differences in white matter degeneration between sporadic ALS and a unique familial form of the disease, indicating that genotype influences the distribution of cerebral pathologic features in ALS.
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| 2. |
- van Es, Michael A, et al.
(författare)
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Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1083-1087
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a genome-wide association study among 2,323 individuals with sporadic amyotrophic lateral sclerosis (ALS) and 9,013 control subjects and evaluated all SNPs with P < 1.0 x 10(-4) in a second, independent cohort of 2,532 affected individuals and 5,940 controls. Analysis of the genome-wide data revealed genome-wide significance for one SNP, rs12608932, with P = 1.30 x 10(-9). This SNP showed robust replication in the second cohort (P = 1.86 x 10(-6)), and a combined analysis over the two stages yielded P = 2.53 x 10(-14). The rs12608932 SNP is located at 19p13.3 and maps to a haplotype block within the boundaries of UNC13A, which regulates the release of neurotransmitters such as glutamate at neuromuscular synapses. Follow-up of additional SNPs showed genome-wide significance for two further SNPs (rs2814707, with P = 7.45 x 10(-9), and rs3849942, with P = 1.01 x 10(-8)) in the combined analysis of both stages. These SNPs are located at chromosome 9p21.2, in a linkage region for familial ALS with frontotemporal dementia found previously in several large pedigrees.
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| 3. |
- Johnston, James B., et al.
(författare)
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Targeting the EGFR pathway for cancer therapy
- 2006
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Ingår i: Current Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 0929-8673 .- 1875-533X. ; 13:29, s. 3483-3492
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Tidskriftsartikel (refereegranskat)abstract
- Clinical studies have shown that HER-2/Neu is over-expressed in up to one-third of patients with a variety of cancers, including B-cell acute lymphoblastic leukemia (B-ALL), breast cancer and lung cancer, and that these patients are frequently resistant to conventional chemo-therapies. Additionally, in most patients with multiple myeloma, the malignant cells over-express a number of epidermal growth factor receptors (EGFR)s and their ligands, HB-EGF and amphiregulin, thus this growth-factor family may be an important aspect in the patho-biology of this disease. These and other, related findings have provided the rationale for the targeting of the components of the EGFR signaling pathways for cancer therapy. Below we discuss various aspects of EGFR-targeted therapies mainly in hematologic malignancies, lung cancer and breast cancer. Beside novel therapeutic approaches, we also discuss specific side effects associated with the therapeutic inhibition of components of the EGFR-pathways. Alongside small inhibitors, such as Lapatinib (Tykerb, GW572016), Gefitinib (Iressa, Z131839), and Erlotinib (Tarceva, OSI-774), a significant part of the review is also dedicated to therapeutic antibodies (e.g.: Trastuzumab / Herceptin, Pertuzumab / Omnitarg / rhuMab-2C4, Cetuximab / Erbitux / IMC-C225, Panitumumab / Abenix / ABX-EGF, and also ZD6474). In addition, we summarize, both current therapy development driven by antibody-based targeting of the EGFR-dependent signaling pathways, and furthermore, we provide a background on the history and the development of therapeutic antibodies.
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| 4. |
- Lindblad-Toh, Kerstin, et al.
(författare)
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Genome sequence, comparative analysis and haplotype structure of the domestic dog.
- 2005
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 438:7069, s. 803-19
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Tidskriftsartikel (refereegranskat)abstract
- Here we report a high-quality draft genome sequence of the domestic dog (Canis familiaris), together with a dense map of single nucleotide polymorphisms (SNPs) across breeds. The dog is of particular interest because it provides important evolutionary information and because existing breeds show great phenotypic diversity for morphological, physiological and behavioural traits. We use sequence comparison with the primate and rodent lineages to shed light on the structure and evolution of genomes and genes. Notably, the majority of the most highly conserved non-coding sequences in mammalian genomes are clustered near a small subset of genes with important roles in development. Analysis of SNPs reveals long-range haplotypes across the entire dog genome, and defines the nature of genetic diversity within and across breeds. The current SNP map now makes it possible for genome-wide association studies to identify genes responsible for diseases and traits, with important consequences for human and companion animal health.
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