• Biomolecules & Therapeutics
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• 제11권4호
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• pp.205-213
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• 2003

Various angiogenesis inhibitors target vascular endothelial cells and block tumor angiogenesis. Angiostatin is a specific endogenous angiogenesis inhibitor in clinical trials, which contains only the first four triple loop structures, known as kringle domains. Its generated by proteolytic cleavage of its parent molecule plasminogen, which itself does not exhibit antiangiogenic activity. Kringle domains from prothrombin, apolipoprotein, hepatocyte growth factor, urokinase and tissue-type plasminogen activator also elicit anti-angiogenic or antitumor activities in several model systems, albeit low amino acid sequence identity between angiostatin and each individual kringle. However, the differential effects of each kringle domain on endothelial cell proliferation, and migration observed in these kringle domains, suggest that the amino acid sequence of the primary structure is still important although kringle architecture is essential for anti-mlgiogenic activity. If it is further studied as to how amino acid sequence and kringle architecture contributes in anti-angiogenic activity, with studies on underlying mechanisms of anti-angiogenesis by kringle-based angiogenesis inhibitors, it will provide basis for the development of new potent anti-angiogenesis inhibitors and improvement of the efficacy of angiogenesis inhibitors.

• Journal of Korean Neurosurgical Society
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• 제64권2호
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• pp.207-216
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• 2021

Objective : Rapid dissolution of blood clots reduces vasospasm and hydrocephalus after subarachnoid hemorrhage (SAH), and locally administered fibrinolytic drugs (LAFDs) could facilitate the dissolution. However, the efficacy of LAFDs remains controversial. The aim of this meta-analysis was to determine the efficacy of LAFDs for vasospasm and hydrocephalus and in clinical outcomes. Methods : From PubMed, EMBASE, and Cochrane database, data were extracted by two authors. Meta-analysis was performed using a random effect model. Inclusion criteria were patients who had LAFDs with urokinase-type or recombinant tissue-plasminogen activator after SAH in comparison with medically untreated patients with fibrinolytic drugs. We only included randomized controlled trials (RCTs) in this analysis. The outcomes of interest were vasospasm, hydrocephalus, mortality, and 90-day unfavorable functional outcome. Results : Data from eight RCTs with 550 patients were included. Pooled-analysis revealed that the LAFDs were significantly associated with lower rates of vasospasm (LAFDs group vs. control group, 26.5% vs. 39.2%; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.32-0.73); hydrocephalus (LAFDs group vs. control group, 26.0% vs. 31.6%; OR, 0.54; 95% CI, 0.32-0.91); and mortality (LAFDs group vs. control group, 10.5% vs. 15.7%; OR, 0.58; 95% CI, 0.34-0.99). The proportion of 90-day unfavorable outcomes was lower in the LAFDs group (LAFDs group vs. control group, 32.7% vs. 43.5%; OR, 0.55; 95% CI, 0.37-0.80). Conclusion : This meta-analysis with eight RCTs indicated that LAFDs were significantly associated with lower rates of vasospasm and hydrocephalus after SAH. Thus, LAFDs could consequently reduce mortality and improve clinical outcome after SAH.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6219-6225
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• 2014

Background: Increasing evidence from animal, epidemiological and clinical investigations suggest that dietary anthocyanins have potential to prevent chronic diseases, including cancers. It is also noteworthy that human epidermal growth factor receptor 2 (ErbB2) protein overexpression or ErbB2 gene amplification has been included as an indicator for metastasis and higher risk of recurrence for breast cancer. Materials and Methods: The present experiments investigated the anti-metastasis effects of black rice anthocyanins (BRACs) on ErbB2 positive breast cancer cells in vivo and in vitro. Results: Oral administration of BRACs (150 mg/kg/day) reduced transplanted tumor growth, inhibited pulmonary metastasis, and decreased lung tumor nodules in BALB/c nude mice bearing ErbB2 positive breast cancer cell MDA-MB-453 xenografts. The capacity for migration, adhesion, motility and invasion was also inhibited by BRACs in MDA-MB-453 cells in a concentration dependent manner, accompanied by decreased activity of a transfer promoting factor, urokinase-type plasminogen activator (u-PA). Conclusions: Together, our results indicated that BRACs possess anti-metastasis potential against ErbB2 positive human breast cancer cells in vivo and in vitro through inhibition of metastasis promoting molecules.

• Molecules and Cells
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• 제40권10호
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• pp.761-772
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• 2017

Glioblastoma is the most frequent and most aggressive brain tumor in adults. Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but not present in other human normal tissues or in gliomas. Therefore, we hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism. The glioblastoma U87MG cells stably transfected with the lentivirus plasmid containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed. In the present study, we found that the tumorigenicity of U87MG in nude mice was totally inhibited by SLC8A2. Overexpression of SLC8A2 had no effect on cell proliferation or cell cycle, but impaired the invasion and migration of U87MG cells, most likely through inactivating the extracellular signal-related kinases (ERK)1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding activity of nuclear factor kappa B ($NF-{\kappa}B$), reducing the level of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its receptor (uPAR) system (ERK1/2-$NF-{\kappa}B$-MMPs/uPA-uPAR), and altering the protein levels of epithelial to mesenchymal transitions (EMT)-associated proteins E-cardherin, vimentin and Snail. In addition, SLC8A2 inhibited the angiogenesis of U87MG cells, probably through combined inhibition of endothelium-dependent and endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2 serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth of glioblastoma.

• Clinical and Experimental Reproductive Medicine
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• 제33권4호
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• pp.229-236
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• 2006

목 적: 자궁내막증에서 그 병태생리를 연구함에 있어서 fibrinolytic system과의 연관성을 알아보기 위해서 자궁내막증 환자와 자궁내막증이 아닌 대조군의 자궁내막에서 urokinase plasminogen activator (u-PA)와 urokinase type plasminogen activator receptor (u-PAR)의 mRNA의 발현의 차이를 알아보고자 하였다. 연구방법: 본원 산부인과를 방문한 한국인 여성 중 수술을 통해 자궁내막증을 진단 받은 33명의 환자와 난소 낭종 등의 양성 질환으로 개복술이나 골반경 수술을 시행한 환자 중 자궁내막증이 없음을 확인한 여성 32명을 대조군으로 하였다. 각각의 대상으로부터 얻은 자궁내막 조직에서 RNA를 추출하여 RT-QC PCR을 시행하여 얻고자 하는 대상의 mPNA 양을 정량화하여 두 군 간에 차이가 있는지를 생리주기에 따라 비교하였다. 결 과: u-PA와 u-PAR의 mPNA는 자궁내막증 환자 및 대조군에서 모두 발현하였으며, 자궁내막증 환자에서의 u-PA mPNA는 증식기 자궁내막에서 대조군에 비해 통계적으로 유의하게 높게 발현됨을 관찰하였다. u-PAR mPNA는 두 군 사이에서 생리주기 전반에 걸쳐 비교했을 때 통계적으로 유의한 차이는 없었다. 결 론: 자궁내막증의 병태생리와 관련하여 u-PA와 u-PAR의 mPNA 발현에 대해서 조사한 결과 u-PA mPNA가 자궁내막증 환자에서 대조군보다 통계적으로 유의하게 높게 발현되었고 이것은 자궁내막증 환자의 자궁내막의 성격이 좀 더 침습적이고, 이로써 복막에의 침습에도 더 유리한 역할을 가진다고 볼 수 있다. 자궁내막증에 대한 기본적인 병태생리로 볼 때, 자궁내막 자체가 가장 중요한 역할을 하리라고 보며, 이를 단백질 분해능과 연관지어 생각해 볼 때, u-PA 발현의 dysregulation이 자궁내막의 침습에 중요한 병태생리라고 생각된다.