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1.
Cancer Sci ; 99(10): 1940-9, 2008 Oct.
Article in English | MEDLINE | ID: mdl-19016753

ABSTRACT

Anaplastic thyroid carcinoma (ATC) is one of the most virulent of all human malignancies, with a mean survival time among patients of less than 1 year after diagnosis. To date, however, cytogenetic information on this disease has been very limited. During the course of a program to screen a panel of ATC cell lines for genomic copy-number aberrations using array-based comparative genomic hybridization, we identified a high-level amplification of the ITCH gene, which is mapped to 20q11.22 and belongs to the homologous to the E6-associated protein carboxylterminus ubiquitin ligase family. The expression of ITCH was increased in 4 of 14 ATC cell lines (28.6%), including 8305C in which there was a copy-number amplification of this gene, and six of seven primary cases (85.7%). Among the primary thyroid tumors, a considerable number of ITCH high expressers was found in ATC (40/45, 88.9%), papillary thyroid carcinoma (25/25, 100%), and papillary microcarcinoma (25/25, 100%). Furthermore, knockdown of ITCH by specific small interfering RNA significantly inhibited the growth of ITCH-overexpressing cells, whereas ectopic overexpression of ITCH promoted growth of ATC cell lines with relatively weak expression. These observations indicate ITCH to be the most likely target for 20q11.22 amplification and to play a crucial role in the progression of thyroid carcinoma.


Subject(s)
Chromosomes, Human, Pair 20 , Gene Amplification , Repressor Proteins/genetics , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Ubiquitin-Protein Ligases/genetics , Carcinoma/genetics , Carcinoma/metabolism , Carcinoma/pathology , Cell Line, Tumor , Comparative Genomic Hybridization , Gene Expression Regulation, Neoplastic , Humans , Oligonucleotide Array Sequence Analysis , Thyroid Neoplasms/metabolism
2.
Tokai J Exp Clin Med ; 29(1): 7-12, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15449806

ABSTRACT

Low-dose aspirin (acetylsalicylic acid 81 mg/day, LDA) is often used as an antiplatelet drug in the treatment of cardiovascular and cerebrovascular diseases as well as for patients with anti-phospholipid antibody syndrome. In this study, we explored the duration of the inhibitory effect of a single LDA on platelet aggregation, using the newly developed aggregometry with the laser light scattering method. Five healthy volunteers (females between 23 and 30 years old) ingested 81 mg of buffered aspirin. Platelet aggregation was measured with adenosine 5'-diphosphate before the ingestion and at the 1st, 2nd, 4th, 6th, and 8th day thereafter. The results showed that the effect of 81 mg of aspirin continues for at least 8 days, which suggested that the intermittent administration of 81 mg of aspirin (a few times a week) might be an alternative way to induce the anti-platelet effect.


Subject(s)
Aspirin/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Platelet Aggregation/drug effects , Platelet Function Tests , Adult , Aspirin/administration & dosage , Female , Humans , Needles , Platelet Aggregation Inhibitors/administration & dosage , Time Factors
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