• Journal of Yeungnam Medical Science
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• 제23권2호
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• pp.143-151
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• 2006

In the past decade, the median duration of survival among patients with advanced colorectal cancer has increased from 12 months to about 18 months, primarily as a results of the introduction of irinotecan and oxaliplatin. Advances in the understanding of the molecular mechanisms underlying the development and progression of cancer have resulted in the discovery of new therapeutic interventions that target specific molecular abnormalities. Their specificity, and therefore their potential to bind preferentially and modify tumor-specific targets, sparing normal tissues and causing fewer side-effects compared to conventional cytotoxic agents, makes them an attractive therapeutic option. The future of this approach for the treatment of solid tumors is promising.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.173.1-173.1
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• 2003

One of attractive target for Rheumatoid Arthritis (RA) therapy is the cytokine, tumor necrosis factor-alpha (TNF-$\alpha$), which has been shown to be overproduced in the joint of RA patients. The clinical success of anti- TNFR biologics has validated TNF-$\alpha$ as a drug discovery target. Thus, inhibiting of formation of TNF-$\alpha$ has been emerged to an intriguing approach for RA therapy. TNF-$\alpha$ is processed from its membrane bound precursor by the metalloprotease TNF-$\alpha$ converting enzyme (TACE), Here, biological evaluation, mode of action of natural TACE inhibitor, Gelastatin hydroxamate, are addressed. (omitted)

• 대한방사성의약품학회지
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• 제6권2호
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• pp.139-145
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• 2020

Polo-like kinase 1 (Plk1) is a key protein in mitosis and has been validated as a target for tumor therapy. It is well known to highly overexpress in many kinds of tumor, which has been implicated as a potential biomarker for tumor treatment and diagnosis. Plk1 consists of two domains, the N-terminus kinase domain and the C-terminus polo-box domain (PBD). The inhibitors have been developed for PBD of Plk1, which were shown a high level of affinity and selectivity for Plk1 that led to mitotic arrest and apoptotic cell death. This review discusses the inhibitors for PBD of Plk1 that are suitable for in vivo tumor treatment. They can be further extended for developing in vivo imaging probes for early diagnosis of tumor.

• Genomics & Informatics
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• 제3권4호
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• pp.172-174
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• 2005

Recent anti-cancer approaches have been based to target tumor-specifically associated and/or causative molecules such as RNAs or proteins. As this specifically targeted anti-cancer modulator, we have previously described a novel human cancer gene therapeutic agent that is Tetrahymena group I intron-based trans-splicing ribozyme which can reprogram and replace human telomerase reverse transcriptase (hTERT) RNA to selectively induce tumor-specific cytotoxicity in cancer cells expressing the target RNA. Moreover, the specific ribozyme has been shown to efficiently retard tumor tissues in xenograft mice which had been inoculated with hTERT-expressing human cancer cells. In this study, we assessed specificity of trans-splicing reaction in cells to evaluate the therapeutic feasibility of the specific ribozyme. In order to analyze the trans-spliced products by the specific ribozyme in hTERT-positive cells, RT, 5'-end RACE-PCR, and sequencing reactions of the spliced RNAs were employed. Then, whole analyzed products resulted from reactions only with the hTERT RNA. This study suggested that the developed ribozyme perform highly specific RNA replacement of the target RNA in cells, hence trans-splicing ribozyme will be one of specific agents for genetic approach to revert cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2789-2800
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• 2013

Background: The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. Material and Method: A systematic literature search was performed for original articles published from January 2007 until May 2012. Results: Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. $Wnt/{\beta}$-catenin signaling pathway has been also evidenced to be an attractive CSC-target. Conclusions: This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3711-3719
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• 2016

Drawbacks of conventional cancer treatments, with lack of specificity and cytotoxicity using current approaches, underlies the necessity for development of a novel approach, gene-directed cancer therapy. This has provided novel technological opportunities in vitro and in vivo. This review focuses on a member of an apoptosis inhibitor family, survivin, as a valuable target. Not only the gene but also its promoter are applicable in this context. This article is based on a literature survey, with especial attention to RNA interference as well as tumor-specific promoter action. The search engine and databases utilized were Science direct, PubMed, MEDLINE and Google. In addition to cell-cycle modulation, apoptosis inhibition, interaction in cell-signaling pathways, cancer-selective expression, survivin also may be considered as specific target through its promoter as a novel treatment for cancer. Our purpose in writing this article was to create awareness in researchers, emphasizing relation of survivin gene expression to potential cancer treatment. The principal result and major conclusion of this manuscript are that survivin structure, biological functions and applications of RNA interference systems as well as tumor-specific promoter activity are of major interest for cancer gene therapy.

• Asian Pacific Journal of Cancer Prevention
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• 제15권5호
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• pp.2313-2318
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• 2014

Peroxisome proliferator-activated receptor gamma (PPAR-${\gamma}$), a ligand-dependent nuclear transcription factor, has been found to widely exist in tumor tissues and plays an important role in affecting tumor cell growth. In this study, we investigated the effect of PPAR-${\gamma}$ on aspects of the cervical cancer malignant phenotype, such as cell proliferation and apoptosis. Cell growth assay, Western blotting, Annexin V and flow cytometry analysis consistently showed that treatment with troglitazone (TGZ, a PPAR-${\gamma}$ agonist) led to dose-dependent inhibition of cervical cancer cell growth through apoptosis, whereas T0070907 (another PPAR-${\gamma}$ antagonist) had no effect on Hela cell proliferation and apoptosis. Furthermore, we also detected the protein expression of p53, p21 and Mdm2 to explain the underlying mechanism of PPAR-${\gamma}$ on cellular apoptosis. Our work, finally, demonstrated the existence of the TGZ-PPAR-${\gamma}$-p53 signaling pathway to be a critical regulator of cell apoptosis. These results suggested that PPAR-${\gamma}$ may be a potential therapeutic target for cervical cancer.

• 대한의생명과학회지
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• 제18권3호
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• pp.210-217
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• 2012

Oncolytic viral vectors have shown good candidates for cancer treatment but have many limitations. To improve the therapeutic potential of oncolytic vaccinia virus, we developed a recombinant vaccinia virus expressing the 4-1BBL co-stimulatory molecule or CCL21. 4-1BBL and CCL21 expression was identified by FACS analysis and immunoblotting. rV-4-1BBL vaccination shows significant tumor regression compared to rV-LacZ, but rV-CCL21 shows rapid tumor growth compared to rV-LacZ in the poorly immunogenic B16 murine melanoma model. 4-1BBL expression resulted in the increase of the number of CD8+ T cells and especially the increase of effector (CD62L-CD44+) CD8+ T cells. These data suggest 4-1BBL may be the potential target for enhancement of tumor immunotherapy.

• 대한방사선치료학회지
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• 제28권2호
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• pp.139-148
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• 2016

목 적 : 양성자 치료 시 사용되는 Range Compensator는 Target의 Distal Margin의 선량에 대해 정상조직에 전달되는 양성자 빔 선량을 보정하는 역할을 한다. 이에 뇌종양 치료에 사용되는 Range Compensator의 Smooth Thickness를 다르게 적용함에 따른 PTV와 OAR의 선량을 비교하여 대상 부위의 선량이 개선되는 것을 확인해 보고자 한다. 대상 및 방법 : 본원에서 양성자 치료를 받은 뇌종양 환자 10명을 대상으로 Eclipse Proton Planning System(Version 10.0, Varian, USA)의 Compensator Editor를 사용하여 Range Compensator에 적용되는 Smooth Thickness를 각각 1회에서 5회까지 순차적으로 적용하였다. 치료계획의 알고리즘은 Proton Convolution Superposition(version 8.1.20 or 10.0.28)을 사용하였고, Smooth Thickness를 단계적으로 적용함에 따른 PTV의 Dmax, Dmin, Homogeneity Index, Conformity Index 그리고 종양주위의 OAR 선량을 비교하였다. 결 과 : Smooth Thickness를 1회에서 5회까지 적용하였을 때 PTV의 최대선량(Dmax)은 최대 4.3%, 최소 0.8%, 평균 1.81% 감소하였으며, 최소선량(Dmin)은 최대 1.8%, 최소 0.2%, 평균 0.82% 증가하였고, 최대선량과 최소선량의 차이는 최대 5.9%, 최소 1.4%, 평균 2.63% 감소하였다. Homogeneity Index는 평균 0.018 감소하였고 Conformity Index는 거의 변화가 없었다. OAR 선량은 Brain Stem에서 최대 1.6%, 최소 0.1%, 평균 0.59% 감소하였으며, Optic Chiasm에서 최대 1.3%, 최소 0.3%, 평균 0.45% 감소하였으나, C와 E환자가 각각 0.3%, 0.6% 증가하였다. 그리고 Rt. Optic Nerve에서 최대 1.5%, 최소 0.3%, 평균 0.8% 감소하였으나, B환자가 0.1% 증가하였다. Lt. Optic Nerve에서는 최대 1.8%, 최소 0.3%, 평균 0.67% 감소하였으나, H환자가 0.4% 증가하였다. 결 론 : 뇌종양 환자의 양성자 치료에 사용되는 Range Compensator의 Smooth Thickness가 단계적으로 적용될수록 Compensator의 해상도가 증가하여 가장 최적화된 양성자 빔 선량을 전달할 수 있다. 이는 PTV에 좀 더 균일한 선량을 조사할 수 있고 또한 OAR에 작용하는 불필요한 선량을 감소시켜 부작용을 줄일 수 있을 것으로 사료된다.

• Molecules and Cells
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• 제39권8호
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• pp.619-624
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• 2016

Glioblastoma stem cells (GBM-SCs) are believed to be a subpopulation within all glioblastoma (GBM) cells that are in large part responsible for tumor growth and the high grade of therapeutic resistance that is so characteristic of GBM. MicroRNAs (miR) have been implicated in regulating the expression of oncogenes and tumor suppressor genes in cancer stem cells, including GBM-SCs, and they are a potential target for cancer therapy. In the current study, miR-203 expression was reduced in $CD133^+$ GBM-SCs derived from six human GBM biopsies. MicroRNA-203 transfected GBM-SCs had reduced capacity for self-renewal in the cell sphere assay and increased expression of glial and neuronal differentiation markers. In addition, a reduced proliferation rate and an increased rate of apoptosis were observed. Therefore, miR-203 has the potential to reduce features of stemness, specifically in GBM-SCs, and is a logical target for GBM gene therapy.