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  • 1
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    Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients (1991)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 1991-08-09
    Description: Previous studies suggested that one or more genes on chromosome 5q21 are responsible for the inheritance of familial adenomatous polyposis (FAP) and Gardner's syndrome (GS), and contribute to tumor development in patients with noninherited forms of colorectal cancer. Two genes on 5q21 that are tightly linked to FAP (MCC and APC) were found to be somatically altered in tumors from sporadic colorectal cancer patients. One of the genes (APC) was also found to be altered by point mutation in the germ line of FAP and GS patients. These data suggest that more than one gene on chromosome 5q21 may contribute to colorectal neoplasia, and that mutations of the APC gene can cause both FAP and GS. The identification of these genes should aid in understanding the pathogenesis of colorectal neoplasia and in the diagnosis and counseling of patients with inherited predispositions to colorectal cancer.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Nishisho, I -- Nakamura, Y -- Miyoshi, Y -- Miki, Y -- Ando, H -- Horii, A -- Koyama, K -- Utsunomiya, J -- Baba, S -- Hedge, P -- CA06973/CA/NCI NIH HHS/ -- CA35494/CA/NCI NIH HHS/ -- CA44688/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 1991 Aug 9;253(5020):665-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry, Cancer Institute, Tokyo, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1651563" target="_blank"〉PubMed〈/a〉
    Keywords: Adenomatous Polyposis Coli/*genetics ; Amino Acid Sequence ; Base Sequence ; Chromosome Mapping ; *Chromosomes, Human, Pair 5 ; Codon/genetics ; Colonic Neoplasms/*genetics ; DNA, Neoplasm/genetics/isolation & purification ; Genetic Linkage ; Genetic Variation ; Humans ; Molecular Sequence Data ; *Mutation ; Oligonucleotide Probes ; Polymerase Chain Reaction/methods ; Rectal Neoplasms/*genetics
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
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  • 2
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    Identification of a primary target of thalidomide teratogenicity (2010)
    American Association for the Advancement of Science (AAAS)
    Details
    Publication Date: 2010-03-13
    Description: Half a century ago, thalidomide was widely prescribed to pregnant women as a sedative but was found to be teratogenic, causing multiple birth defects. Today, thalidomide is still used in the treatment of leprosy and multiple myeloma, although how it causes limb malformation and other developmental defects is unknown. Here, we identified cereblon (CRBN) as a thalidomide-binding protein. CRBN forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1) and Cul4A that is important for limb outgrowth and expression of the fibroblast growth factor Fgf8 in zebrafish and chicks. Thalidomide initiates its teratogenic effects by binding to CRBN and inhibiting the associated ubiquitin ligase activity. This study reveals a basis for thalidomide teratogenicity and may contribute to the development of new thalidomide derivatives without teratogenic activity.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Ito, Takumi -- Ando, Hideki -- Suzuki, Takayuki -- Ogura, Toshihiko -- Hotta, Kentaro -- Imamura, Yoshimasa -- Yamaguchi, Yuki -- Handa, Hiroshi -- New York, N.Y. -- Science. 2010 Mar 12;327(5971):1345-50. doi: 10.1126/science.1177319.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Integrated Research Institute, Tokyo Institute of Technology, Yokohama 226-8503, Japan.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/20223979" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Carrier Proteins/metabolism ; Chick Embryo ; Cullin Proteins/metabolism ; DNA-Binding Proteins/*metabolism ; Embryo, Nonmammalian/drug effects ; Embryonic Development/drug effects ; Fibroblast Growth Factors/genetics/metabolism ; Forelimb/abnormalities/embryology ; Gene Expression Regulation, Developmental ; HeLa Cells ; Humans ; Mutant Proteins/metabolism ; Peptide Hydrolases/genetics/*metabolism ; Teratogens/metabolism/*toxicity ; Thalidomide/metabolism/*toxicity ; Ubiquitin-Protein Ligases/antagonists & inhibitors/*metabolism ; Ubiquitination ; Zebrafish/embryology/genetics ; Zebrafish Proteins/genetics/metabolism
    Print ISSN: 0036-8075
    Electronic ISSN: 1095-9203
    Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics
    Published by American Association for the Advancement of Science (AAAS)
    Location Call Number Expected Availability
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