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    • 23. 发明申请
    • TUMOR SUPPRESSOR LOCUS IN PROSTATE CANCER
    • 肿瘤抑制剂位于前列腺癌中
    • WO2003097843A1
    • 2003-11-27
    • PCT/US2003/015208
    • 2003-05-14
    • HENRY M. JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINEZOU, ChiqiangSUN, MeiSRIVASTAVA, ShivMOUL, Judd, W.
    • ZOU, ChiqiangSUN, MeiSRIVASTAVA, ShivMOUL, Judd, W.
    • C12N15/85
    • C07K14/4703A61K48/00
    • The long arm of chromosome 6 is frequently deleted in diverse human neoplasm. Studies showed a minimum deletion region between markers D6S1056 and D6S300 on chromosome 6q in primary CaP (prostate cancer). Significant association of LOH (loss of heterozygosity) of 6q16 with aging CaP patients and patients with seminal vesicle invasion was shown using LCM (laser capture microdissection)-derived DNA samples from 48 CaP patients. A novel contig designated as 6qTSG1 was generated within a minimal 200 kb region centered around D6S1013. The 6qTSG1 exhibited complex multiple splicing variants with low or absent expression in CaP cells. However, none of the transcripts identified contained a significant open reading frame. Expression of 6qTSG1 was induced in LNCaP cells that were cultured in charcoal-stripped serum medium suggesting an up-regulation of 6qTSG1 by androgen ablation. Induction of 6qTSGl expression in response to androgen ablation was abrogated in androgen independent derivatives of LNCaP cells. The 6qTSG1 inhibited tumor cell growth after transfection into PC3 cells. A candidate CaP suppressor locus was identified on chromosome 6q16.1, of which alteration linked to CaP progression.
    • 染色体6的长臂在不同的人类肿瘤中经常被删除。 研究显示原代CaP(前列腺癌)染色体6q上的标记D6S1056和D6S300之间的最小缺失区。 使用来自48名CaP患者的LCM(激光捕获显微切割)衍生的DNA样品,显示6q16的LOH(杂合性的丧失)与老化的CaP患者和精囊浸润患者的显着关联。 在以D6S1013为中心的最小200kb区域内产生了称为6qTSG1的新型重叠群体。 6qTSG1表现出在CaP细胞中具有低表达或缺失表达的复合多个剪接变体。 然而,没有一个确认的成绩单包含一个重要的开放阅读框架。 在用炭活化血清培养基培养的LNCaP细胞中诱导6qTSG1的表达,表明通过雄激素消融上调6qTSG1。 在雄激素消融中诱导6qTSG1表达在雄激素非依赖性LNCaP细胞衍生物中被消除。 转染PC3细胞后,6qTSG1抑制肿瘤细胞生长。 在染色体6q16.1上鉴定出候选CaP抑制基因座,其与CaP进展有关。