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    • 2. 发明申请
    • ENDOGENOUS GRANZYME B IN HUMAN NON-HEMATOPOIETIC CELLS
    • 人非球形细胞中的内源性GRANZYME B
    • WO2004028342A2
    • 2004-04-08
    • PCT/US2003/029967
    • 2003-09-24
    • BOARD OF REGENTS, THE UNIVERSITY OF TEXAS SYSTEMXU, Hong-JiJU, Shi-XueMILLS, Gordon, B.
    • XU, Hong-JiJU, Shi-XueMILLS, Gordon, B.
    • A61B
    • C12N9/6467
    • The instant invention relates to the determination that constitutively nearly silent GrB locus in human breast carcinoma and osteosarcoma cells activated upon retinoblastoma protein (pRB)-induced growth arrest owing to the usage of an alternative promoter/transcription start site. Cloned novel cDNA from the locus adds 34 amino acid residues to the N-terminus of GrB zymogen. The alternate product has been designated as GrB-NIC. Tumor cells with accumulated endogenous GrB-NIC, whose mature form was identical to lymphocyte GrB but with a distinctive glycosylation pattern, undergoes post-growth-arrest apoptosis that occurs concurrently with pRB cleavage, and are capable of inducing rapid apoptosis of bystander pRB - tumor cells. Expression of GrB-NIC is also observed in malignant cells of other types as well as in normal non-immune cells upon cell differentiation, especially in differentiating and differentiated neural cells. GrB-NIC plays a physiological role in embryonic, and particularly in early neuronal development. The disclosure further provides compositions and methods utilizing this new GrB-NIC technology.
    • 本发明涉及由于使用替代性启动子/转录起始位点,人乳腺癌和骨肉瘤细胞中组成型几乎无声的GrB基因座在视网膜母细胞瘤蛋白(pRB)上激活的生长停滞的测定。 来自该基因座的克隆的新的cDNA向GrB酶原的N末端添加34个氨基酸残基。 备用产品已被指定为GrB-NIC。 具有积累的内源性GrB-NIC的肿瘤细胞,其成熟形式与淋巴细胞GrB相同但具有独特的糖基化模式,经历与pRB切割同时发生的后生长停滞的凋亡,并且能够诱导旁观者pRB < >肿瘤细胞。 在细胞分化,特别是分化和分化的神经细胞中,其他类型的恶性细胞以及正常的非免疫细胞也观察到GrB-NIC的表达。 GrB-NIC在胚胎中起着生理作用,特别是在早期神经元发育中。 本公开进一步提供了使用该新型GrB-NIC技术的组合物和方法。
    • 3. 发明申请
    • ENDOGENOUS GRANZYME B IN HUMAN NON-HEMATOPOIETIC CELLS
    • 人非球形细胞中的内源性GRANZYME B
    • WO2004028342A3
    • 2007-12-06
    • PCT/US0329967
    • 2003-09-24
    • UNIV TEXASXU HONG-JIJU SHI-XUEMILLS GORDON B
    • XU HONG-JIJU SHI-XUEMILLS GORDON B
    • A01N43/04A61B20060101A61K31/70C07H21/04C12N5/00C12N5/02C12N9/64C12N15/00
    • C12N9/6467
    • The instant invention relates to the determination that constitutively nearly silent GrB locus in human breast carcinoma and osteosarcoma cells activated upon retinoblastoma protein (pRB)-induced growth arrest owing to the usage of an alternative promoter/transcription start site. Cloned novel cDNA from the locus adds 34 amino acid residues to the N-terminus of GrB zymogen. The alternate product has been designated as GrB-NIC. Tumor cells with accumulated endogenous GrB-NIC, whose mature form was identical to lymphocyte GrB but with a distinctive glycosylation pattern, undergoes post-growth-arrest apoptosis that occurs concurrently with pRB cleavage, and are capable of inducing rapid apoptosis of bystander pRB - tumor cells. Expression of GrB-NIC is also observed in malignant cells of other types as well as in normal non-immune cells upon cell differentiation, especially in differentiating and differentiated neural cells. GrB-NIC plays a physiological role in embryonic, and particularly in early neuronal development. The disclosure further provides compositions and methods utilizing this new GrB-NIC technology.
    • 本发明涉及由于使用替代性启动子/转录起始位点,人乳腺癌和骨肉瘤细胞中组成型几乎无声的GrB基因座在视网膜母细胞瘤蛋白(pRB)上激活的生长停滞的测定。 来自该基因座的克隆新的cDNA向GrB酶原的N末端添加34个氨基酸残基。 备用产品已被指定为GrB-NIC。 具有积累的内源性GrB-NIC的肿瘤细胞,其成熟形式与淋巴细胞GrB相同但具有独特的糖基化模式,经历与pRB切割同时发生的后生长停滞的凋亡,并且能够诱导旁观者pRB - 肿瘤细胞。 在细胞分化,特别是分化和分化的神经细胞中,其他类型的恶性细胞以及正常的非免疫细胞也观察到GrB-NIC的表达。 GrB-NIC在胚胎中起着生理作用,特别是在早期神经元发育中。 本公开进一步提供了使用该新型GrB-NIC技术的组合物和方法。