Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q 14-q 16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent stu...Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q 14-q 16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the 6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approaches showed that U50 underwent frequent genomic deletion and transcriptional downregulation in cell lines derived from breast cancer. Mutation screening identified the same 2-bp deletion of U50 as in prostate cancer in both cell lines and primary tumors from breast cancer, and the deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstrated that, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breast cancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggest that noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.展开更多
目的观察κ阿片受体选择性激动剂(U50,488H)对大鼠心脏缺血/再灌注(ischemia and reperfusion,I/R)室性心律失常的影响并探讨其可能的机制。方法观察U50,488H对大鼠I/R整体动物模型血浆肌酸磷酸激酶(CK)、乳酸脱氢酶(LDH)水平的影响;分...目的观察κ阿片受体选择性激动剂(U50,488H)对大鼠心脏缺血/再灌注(ischemia and reperfusion,I/R)室性心律失常的影响并探讨其可能的机制。方法观察U50,488H对大鼠I/R整体动物模型血浆肌酸磷酸激酶(CK)、乳酸脱氢酶(LDH)水平的影响;分离正常大鼠心脏,采用Langen-dorff离体心脏灌流方法,预先给予U50,488H(5mmol·L-1)和NE(100μmol·L-1),测定其对血流动力学指标和对心律失常的影响;常规酶解法分离成年大鼠心室肌细胞,采用全细胞膜片钳技术观察U50,488H对钠电流的作用。结果①U50+I/R组血浆中CK和LDH的含量较I/R组明显降低(P<0.01)。②与I/R组相比,给予U50,488H后,心率明显下降(P<0.05)。③对照组偶发早搏,I/R组心律失常发生频率明显增加,与I/R组相比较,I/R+NE组心律失常评分明显增高(P<0.01);如果提前给予U50,488H,发现不仅可以明显降低I/R组缺血和再灌注期间室速和室颤的发生率(P<0.01)及降低I/R组心律失常的评分,而且明显降低I/R+NE组心律失常的评分(P<0.01)。④U50,488H(100μmol·L-1)可以明显降低心室肌细胞的钠电流(P<0.01)。结论κ阿片受体激动剂U50,488H对I/R时的心律失常有拮抗作用,其作用可能是通过抑制心肌细胞的钠电流而实现的。展开更多
基金supported in part by a grant from the National Cancer Institute,USA (No. R01CA085560)
文摘Deletion of chromosome 6q is frequent in breast cancer, and the deletion often involves a region in 6q 14-q 16. At present, however, the underlying tumor suppressor gene has not been established. Based on a recent study identifying snoRNA U50 as a candidate for the 6q14-16 tumor suppressor gene in prostate cancer, we investigated whether U50 is also involved in breast cancer. PCR-based approaches showed that U50 underwent frequent genomic deletion and transcriptional downregulation in cell lines derived from breast cancer. Mutation screening identified the same 2-bp deletion of U50 as in prostate cancer in both cell lines and primary tumors from breast cancer, and the deletion was both somatic and in germline. Genotyping of a cohort of breast cancer cases and controls for the mutation demonstrated that, while homozygous genotype of the mutation was rare, its heterozygous genotype occurred more frequently in women with breast cancer. Functionally, re-expression of U50 resulted in the inhibition of colony formation in breast cancer cell lines. These results suggest that noncoding snoRNA U50 plays a role in the development and/or progression of breast cancer.
文摘目的观察κ阿片受体选择性激动剂(U50,488H)对大鼠心脏缺血/再灌注(ischemia and reperfusion,I/R)室性心律失常的影响并探讨其可能的机制。方法观察U50,488H对大鼠I/R整体动物模型血浆肌酸磷酸激酶(CK)、乳酸脱氢酶(LDH)水平的影响;分离正常大鼠心脏,采用Langen-dorff离体心脏灌流方法,预先给予U50,488H(5mmol·L-1)和NE(100μmol·L-1),测定其对血流动力学指标和对心律失常的影响;常规酶解法分离成年大鼠心室肌细胞,采用全细胞膜片钳技术观察U50,488H对钠电流的作用。结果①U50+I/R组血浆中CK和LDH的含量较I/R组明显降低(P<0.01)。②与I/R组相比,给予U50,488H后,心率明显下降(P<0.05)。③对照组偶发早搏,I/R组心律失常发生频率明显增加,与I/R组相比较,I/R+NE组心律失常评分明显增高(P<0.01);如果提前给予U50,488H,发现不仅可以明显降低I/R组缺血和再灌注期间室速和室颤的发生率(P<0.01)及降低I/R组心律失常的评分,而且明显降低I/R+NE组心律失常的评分(P<0.01)。④U50,488H(100μmol·L-1)可以明显降低心室肌细胞的钠电流(P<0.01)。结论κ阿片受体激动剂U50,488H对I/R时的心律失常有拮抗作用,其作用可能是通过抑制心肌细胞的钠电流而实现的。
