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Articles by J. S. Kim
Total Records ( 3 ) for J. S. Kim
  H. J Kim , H. J Lee , H Kim , S. W Cho and J. S. Kim
 

Broad applications of zinc finger nuclease (ZFN) technology—which allows targeted genome editing—in research, medicine, and biotechnology are hampered by the lack of a convenient, rapid, and publicly available method for the synthesis of functional ZFNs. Here we describe an efficient and easy-to-practice modular-assembly method using publicly available zinc fingers to make ZFNs that can modify the DNA sequences of predetermined genomic sites in human cells. We synthesized and tested hundreds of ZFNs to target dozens of different sites in the human CCR5 gene—a co-receptor required for HIV infection—and found that many of these nucleases induced site-specific mutations in the CCR5 sequence. Because human cells that harbor CCR5 null mutations are functional and normal, these ZFNs might be used for (1) knocking out CCR5 to produce T-cells that are resistant to HIV infection in AIDS patients or (2) inserting therapeutic genes at "safe sites" in gene therapy applications.

  H. J Lee , E Kim and J. S. Kim
 

We present a novel approach for generating targeted deletions of genomic segments in human and other eukaryotic cells using engineered zinc finger nucleases (ZFNs). We found that ZFNs designed to target two different sites in a human chromosome could introduce two concurrent DNA double-strand breaks (DSBs) in the chromosome and give rise to targeted deletions of the genomic segment between the two sites. Using this method in human cells, we were able to delete predetermined genomic DNA segments in the range of several-hundred base pairs (bp) to 15 mega-bp at frequencies of 10–3 to 10–1. These high frequencies allowed us to isolate clonal populations of cells, in which the target chromosomal segments were deleted, by limiting dilution. Sequence analysis revealed that many of the deletion junctions contained small insertions or deletions and microhomologies, indicative of DNA repair via nonhomologous end-joining. Unlike other genome engineering tools such as recombinases and meganucleases, ZFNs do not require preinsertion of target sites into the genome and allow precise manipulation of endogenous genomic scripts in animal and plant cells. Thus, ZFN-induced genomic deletions should be broadly useful as a novel method in biomedical research, biotechnology, and gene therapy.

  H. Y Seo , J. M Park , K. H Park , S. J Kim , S. C Oh , B. S Kim , Y. H Kim and J. S. Kim
  Objective

Angiogenesis is one of the crucial steps in various solid tumor growth and metastasis. However, there are limited data regarding the clinical and prognostic significance of serum vascular endothelial growth factor levels per platelet count in unresectable advanced gastric cancer compared with early gastric cancer and healthy volunteers.

Methods

A total of 181 gastric cancer patients were included and control serum samples were acquired from 113 healthy volunteers. The levels of serum vascular endothelial growth factor were measured using human vascular endothelial growth factor quantitative enzyme-linked immunosorbent assay. Survival curves were calculated using the Kaplan–Meier method and survival comparisons were made by the log-rank test in metastatic gastric cancer.

Results

There was a significant correlation between serum vascular endothelial growth factor levels and differentiation of tumor (P = 0.014), stage (P = 0.036). The overall survival (P = 0.0432) and the progression-free survival (P = 0.0116) were significantly shorter in patients with high serum vascular endothelial growth factor per platelet count (≥1.626 pg/106). In the multivariate analysis, the presence of peritoneal carcinomatosis (P = 0.039), serum vascular endothelial growth factor per platelet (P = 0.005) were found to be significantly associated with poor progression-free survival.

Conclusions

This study demonstrates that serum vascular endothelial growth factor per platelet count is correlated with poor overall survival and progression-free survival in patients with advanced gastric cancer.

 
 
 
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