• Asian Pacific Journal of Cancer Prevention
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• 제15권24호
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• pp.10621-10625
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• 2015

Background: Increasing evidence has indicated that high Forkhead box protein C2 (FOXC2) level is closely associated with the development, progression, and poor prognosis of a variety of tumors. However, the relationship between FOXC2 and the progression of human gliomas remains to be clarified. The aim of present study was to assess FOXC2 expression and to explore its contribution in human gliomas. Materials and Methods: Realtime quantitative PCR was performed to examine FOXC2 expression in 85 pairs of fresh frozen glioma tissues and corresponding non-neoplastic brain tissues. Associations of FOXC2 expression with clinicopathological factors and prognosis of glioma patients were statistically analyzed. Results: The relative mRNA expression of FOXC2 was significantly higher in glioma tissues than the corresponding non-neoplastic brain tissues (p<0.001). In addition, high FOXC2 expression was significantly associated with advanced pathological grade (P=0.005) and the low Karnofsky performance score (KPS) (p=0.003), correlating with poor survival (p<0.001). Furthermore, multivariate Cox regression analysis showed that high FOXC2 expression was an independent predictor of overall survival (p=0.006). Conclusions: FOXC2 may act as an oncogenic gene and represent a potential regulator of aggressive development and a candidate prognostic marker in human gliomas.

• KSBB Journal
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• 제20권1호
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• pp.1-11
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• 2005

Recently, there has been extremely active in the research of stem cell biology. Stem cells have excellent potential for being the ultimate source of transplantable cells for many different tissues. Researchers hope to use stem cells to repair or replace diseased or damaged organs, leading to new treatments for human disorders that are currently incurable, including diabetes, spinal cord injury and brain diseases. There are primary sources of stem cells like embryonic stem cells and adult stem cells. Stem cells from embryos were known to give rise to every type of cell. However, embryonic stem cells still have a lot of disadvantages. First, transplanted cells sometimes grow into tumors. Second, the human embryonic stem cells that are available for research would be rejected by a patient's immune system. Tissue-matched transplants could be made by either creating a bank of stem cells from more human embryos, or by cloning a patient's DNA into existing stem cells to customize them. However, this is laborious and ethically contentious. These problems could be overcome by using adult stem cells, taken from a patient, that are treated to remove problems and then put back. Nevertheless, some researchers do not convince that adult stem cells could, like embryonic ones, make every tissue type. Human stem cell research holds enormous potential for contributing to our understanding of fundamental human biology. In this review, we discuss the recent progress in stem cell research and the future therapeutic applications.

• Molecules and Cells
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• 제45권7호
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• pp.479-494
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• 2022

Human mesenchymal stem cells (MSCs) are multipotent stem cells that have been intensively studied as therapeutic tools for a variety of disorders. To enhance the efficacy of MSCs, therapeutic genes are introduced using retroviral and lentiviral vectors. However, serious adverse events (SAEs) such as tumorigenesis can be induced by insertional mutagenesis. We generated lentiviral vectors encoding the wild-type herpes simplex virus thymidine kinase (HSV-TK) gene and a gene containing a point mutation that results in an alanine to histidine substitution at residue 168 (TK(A168H)) and transduced expression in MSCs (MSC-TK and MSC-TK(A168H)). Transduction of lentiviral vectors encoding the TK(A168H) mutant did not alter the proliferation capacity, mesodermal differentiation potential, or surface antigenicity of MSCs. The MSC-TK(A168H) cells were genetically stable, as shown by karyotyping. MSC-TK(A168H) responded to ganciclovir (GCV) with an half maximal inhibitory concentration (IC₅₀) value 10-fold less than that of MSC-TK. Because MSC-TK(A168H) cells were found to be non-tumorigenic, a U87-TK(A168H) subcutaneous tumor was used as a SAE-like condition and we evaluated the effect of valganciclovir (vGCV), an oral prodrug for GCV. U87-TK(A168H) tumors were more efficiently ablated by 200 mg/kg vGCV than U87-TK tumors. These results indicate that MSC-TK(A168H) cells appear to be pre-clinically safe for therapeutic use. We propose that genetic modification with HSV-TK(A168H) makes allogeneic MSC-based ex vivo therapy safer by eliminating transplanted cells during SAEs such as uncontrolled cell proliferation.

• BMB Reports
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• 제49권7호
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• pp.370-375
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• 2016

Ras oncoproteins are small molecular weight GTPases known for their involvement in oncogenesis, which operate in a complex signaling network with multiple effectors. Approximately 25% of human tumors possess mutations in a member of this family. The Raf1/MEK/Erk1/2 pathway is one of the most intensively studied signaling mechanisms. Different levels of regulation account for the inactivation of MAP kinases by MAPK phosphatases in a cell type- and stimuli-dependent manner. In the present study, using three inducible Ras-expressing NIH/3T3 cell lines, we demonstrated that MKP3 upregulation requires the activation of the Erk1/2 pathway, which correlates with the shutdown of this pathway. We also demonstrated, by applying pharmacological inhibitors and effector mutants of Ras, that induction of MKP3 at the protein level is positively regulated by the oncogenic Ras/Raf/MEK/Erk1/2 signaling pathway.

• 한국식품위생안전성학회지
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• 제26권2호
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• pp.150-153
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• 2011

흰자작나무의 껍질에서 발견된 자연적으로 발생한 triterpene 인 betulinic acid (BA)가 다양한 종류의 암세포와 동물 모델에서 세포사멸을 유도하는 것으로 알려져 있다. 하지만 자궁경부암세포에서 BA의 화학적 암예방 효과는 연구되지 않은 상태이다. 따라서 이 연구에서는 사람 자궁경부암세포주인 KB세포를 이용하여, BA가 세포증식을 감소시키고 세포사멸을 유도하는 것을 확인하였다. KB 세포에서 BA에 의해 유도되는 세포증식의 억제는 specificity protein 1 (Sp1)과 Sp1의 표적단백질인 myeloid cell leukemia-1 (Mcl-1) 그리고 survivin의 감소 때문인 것으로 확인되었다. 따라서 BA는 자궁경부암에서 과다 발현되는 Sp1을 조절하는 새로운 화학적 암예방 물질로서 작용할 수 있을 것으로 생각된다.

• Bulletin of the Korean Chemical Society
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• 제25권4호
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• pp.506-510
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• 2004

There have been intensive studies concerning $[^{11}F]$choline ($[^{11}F]$methyldimethyl( ${\beta}$ -hydroxyethyl) ammonium) (1) which is known as a very effective tracer in imaging various human tumors localized in brain, lung, esophagus, rectum, prostate and urinary bladder using Positron Emission Tomography (PET) and there is increasing interest in $^{18}F$ labelled choline (2) and proved to be useful to visualize prostate cancer. We have prepared six $^{18}F$ labelled alkyl choline derivatives (3a-3c, 4a-4c) from ditosylated and dibrominated alkanes in moderate yields. The six alkyl tosylate or bromate ammonium salts have been synthesized as precursors. Radiofluorination was achieved by the treatment of precursors with $^{18}F$ - in the presence of Kryptofix-2.2.2.. The labeling yields varied ranging from 7 to 25%.

• Bulletin of the Korean Chemical Society
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• 제35권10호
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• pp.3030-3034
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• 2014

Bis-chloroethylnitrosourea (BCNU) is currently used as an anti-cancer drug for glioblastoma therapy. In this study, BCNU was loaded into the hydrophobic cores of R3V6 amphiphilic peptide micelles for efficient delivery into brain tumors. The scanning electron microscope (SEM) study showed that the BCNU-loaded R3V6 peptide micelles (R3V6-BCNU) formed spherical micelles. MTT assay showed that R3V6-BCNU more efficiently induced cell death in C6 glioblastoma cells than did BCNU. In the Annexin V assay, R3V6-BCNU more efficiently induced apoptosis than did BCNU alone. Furthermore, the results showed that R3V6 was not toxic to cells. The positive charges of the R3V6 peptide micelles may facilitate the interaction between R3V6-BCNU and the cellular membrane, resulting in an increase in cellular uptake of BCNU. In vivo evaluation with an intracranial glioblastoma rat model showed that R3V6-BCNU more effectively reduced tumor size than BCNU alone. The results suggest that R3V6 peptide micelles may be an efficient carrier of BCNU for glioblastoma therapy.

• Molecules and Cells
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• 제27권3호
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• pp.283-289
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• 2009

Curcumin, a natural compound extracted from rhizomes of curcuma Curcuma species, has been shown to possess potent anti-inflammatory, anti-tumor and anti-oxidative properties. However, the mechanism of action of the compound remains poorly understood. In this report, we have analyzed the effects of curcumin on the cell proliferation of Burkitt's lymphoma Raji cells. The results demonstrated that curcumin could effectively inhibit the growth of Raji cells in a dose- and time-dependent manner. Further studies indicated that curcumin treatment resulted in apoptosis of cells. Biochemical analysis showed that the expression of Bax, Bid and cytochrome C were up-regulated, while the expression of oncogene c-Myc was down regulated after curcumin treatment. Furthermore, poly (ADP-ribose) polymerase (PARP) cleavage was induced by the compound. Interestingly, the antiapoptotic Bcl-2 expression was not significantly changed in Raji cells after curcumin treatment. These results suggested that the mechanism of action of curcumin was to induce mitochondrial damage and therefore led to Raji cell apoptosis. We further investigated the in vivo effects of curcumin on the growth of xenograft tumors in nude mice. The results showed that curcumin could effectively inhibit tumor growth in the xenograft mouse model. The overall results showed that curcumin could suppress the growth of Burkitt's lymphoma cells in both in vitro and in vivo systems.

• Journal of Genetic Medicine
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• 제6권1호
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• pp.1-7
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• 2009

프로모터 CpG island 과메틸화와 히스톤 변경으로 대변되는 후성유전적 변화는 거의 모든 종류의 암에서 발견되는 중요한 발암기전이다. 인간유전자의 60-70% 가량이 프로모터에 CpG islands를 가지고 있으며, 이 유전자들 중 일부가 과메틸화됨으로써 해당유전자의 발현이 차단되고, 종양억제기능이 소실되어 종양세포의 성장을 촉진하게 된다. 암에는 프로모터 CpG island 과메틸화라는 국소적 변화 이외에, 유전체 전반에 걸친 탈메틸화를 동시에 보이는 경우가 대부분인데, 이러한 유전체 저메틸화는 염색체 불안정성과 밀접한 연관관계가 있다. 국소적 과메틸화와 전반적인 저메틸화라는 이러한 상반된 DNA 메틸화 변화는 암세포뿐만 아니라 그 전단계 병변인 이 형성 병변에서도 관찰된다. 프로모터CpG island 과메틸화는 유전자 발현억제 기전으로서의 중요성뿐만 아니라 종양표지자로서의 중요성이 부각되고 있다. 즉, 정상세포에서는 관찰되지 않으면서 암세포에서만 관찰되는 프로모터 CpG island 과메틸화는 암세포의 바이오마커로서의 가치가 있으며, 이를 이용하여 체액에서 암을 진단하려는 시도들이 이루어지고, 이를 활용한 암의 분자진단방법이 개발되고 있다. 또한 이러한 DNA 메틸화는 암환자의 예후 판정이나 항암치료제의 감수성 결정 등에 활용되고 있다. 본 원고에서는 인체 암세포에서의 DNA 메틸화 변화에 관하여 소개하고자 한다.

• Reproductive and Developmental Biology
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• 제30권4호
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• pp.229-234
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• 2006

We have generated transgenic mice that expressed mouse extracellular superoxide dismutase (EC-SOD) in their skin. In particular, the expression plasmid DNA containing human keratin K14 promoter was used to direct the keratinocyte-specific transcription of the transgene. To compare intron-dependent and intron-independent gene expression, we constructed two vectors. The vector B, which contains the rabbit -globin intron 2, was not effective for mouse EC-SOD overexpression. The EC-SOD transcript was detected in the skin, as determined by Northern blot analysis. Furthermore, EC-SOD protein was detected in the skin tissue, as demonstrated by Western blot analysis. To evaluate the expression levels of EC-SOD in various tissues, we purified EC-SOD from the skin, lungs, brain, kidneys, livers, and spleen of transgenic mice and measured its activities. EC-SOD activities in the transgenic mice skin were approximately 7 fold higher than in wild-type mice. These results suggest that the mouse overexpressing vector not only induces keratinocyte-specific expression of EC-SOD, but also expresses successfully functional EC-SOD. Thus, these transgenic mice appeared to be useful for the expression of the EC-SOD gene and subsequent analysis of various skin changes, such as erythema, inflamation, photoaging, and skin tumors.