http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Mutations of <i>ADAMTS9</i> Cause Nephronophthisis-Related Ciliopathy
Choi, Yo Jun,Halbritter, Jan,Braun, Daniela A.,Schueler, Markus,Schapiro, David,Rim, John Hoon,Nandadasa, Sumeda,Choi, Won-il,Widmeier, Eugen,Shril, Shirlee,Kö,rber, Friederike,Sethi, Sidharth K. Elsevier 2019 American journal of human genetics Vol.104 No.1
<P>Nephronophthisis-related ciliopathies (NPHP-RCs) are a group of inherited diseases that are associated with defects in primary cilium structure and function. To identify genes mutated in NPHP-RC, we performed homozygosity mapping and whole-exome sequencing for >100 individuals, some of whom were single affected individuals born to consanguineous parents and some of whom were siblings of indexes who were also affected by NPHP-RC. We then performed high-throughput exon sequencing in a worldwide cohort of 800 additional families affected by NPHP-RC. We identified two <I>ADAMTS9</I> mutations (c.4575_4576del [p.Gln1525Hisfs<SUP>∗</SUP>60] and c.194C>G [p.Thr65Arg]) that appear to cause NPHP-RC. Although ADAMTS9 is known to be a secreted extracellular metalloproteinase, we found that ADAMTS9 localized near the basal bodies of primary cilia in the cytoplasm. Heterologously expressed wild-type ADAMTS9, in contrast to mutant proteins detected in individuals with NPHP-RC, localized to the vicinity of the basal body. Loss of ADAMTS9 resulted in shortened cilia and defective sonic hedgehog signaling. Knockout of <I>Adamts9</I> in IMCD3 cells, followed by spheroid induction, resulted in defective lumen formation, which was rescued by an overexpression of wild-type, but not of mutant, ADAMTS9. Knockdown of <I>adamts9</I> in zebrafish recapitulated NPHP-RC phenotypes, including renal cysts and hydrocephalus. These findings suggest that the identified mutations in <I>ADAMTS9</I> cause NPHP-RC and that ADAMTS9 is required for the formation and function of primary cilia.</P>
김진형,Eugene K. Choi,Hyun-Ki Yoon,Gi-Young Ko,Kyu-Bo Sung,Dong Il Gwon 거트앤리버 소화기연관학회협의회 2010 Gut and Liver Vol.4 No.3
Background/Aims: Despite curative resection, hepatic recurrences cause a significant reduction in survival in patients with primary pancreatic adenocarcinoma. Transcatheter arterial chemoembolization (TACE) has recently been used successfully to treat primary and secondary hepatic malignancy. Methods: Between 2003 and 2008, 15 patients underwent TACE because of hepatic recurrence after curative resection of a pancreatic adenocarcinoma. The tumor response was evaluated based on computed tomography scans after TACE. The overall duration of patient survival was measured. Results: After TACE, a radiographically evident response occurred in six patients whose tumors demonstrated a tumor blush on angiography. Four patients demonstrated stabilization of a hypovascular mass. The remaining five patients demonstrated continued progression of hypovascular hepatic lesions. The median survival periods from the time of diagnosis and from the time of initial TACE were 9.6and 7.5 months, respectively. Conclusions: TACE may represent a viable therapeutic modality in patients with hepatic recurrence after curative resection of pancreatic adenocarcinoma.