• Journal of Embryo Transfer
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• v.25 no.1
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• pp.35-42
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• 2010

Many studies propose that dysfunction of mitochondrial proton-translocating NADH-ubiquinone oxidoreductase (complex I) is associated with neurodegenerative disorders, such as Parkinson's disease and Huntington's disease. Mammalian mitochondrial proton-translocating NADH-quinone oxidoreductase (complex I) consists of at least 46 different subunits. In contrast, the NDI1 gene of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. With a recombinant adeno-associated virus vector carrying the NDI1 gene (rAAV-NDI1) as the gene delivery method, we were able to attain high transduction efficiencies even in the human epithelial cervical cancer cells that are difficult to transfect by lipofection or calcium phosphate precipitation methods. Using a rAAV-NDI1, we demonstrated that the Ndi1 enzyme is successfully expressed in HeLa cells. The expressed Ndi1 enzyme was recognized to be localized in mitochondria by confocal immunofluorescence microscopic analyses and immunoblotting. Using digitonin-permeabilized cells, it was shown that the NADH oxidase activity of the NDI1-transduced HeLa cells were not affected by rotenone which is inhibitor of complex I, but was inhibited by flavone and antimycin A. The NDI1-transduced cells were able to grow in media containing rotenone. In contrast, control cells that did not receive the NDI1 gene failed to survive. In particular, in the NDI1-transduced cells, the yeast enzyme becomes integrated into the human respiratory chain. It is concluded that the NDI1 gene provides a potentially useful tool for gene therapy of mitochondrial diseases caused by complex I deficiency.

• Korean Journal of Head & Neck Oncology
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• v.35 no.1
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• pp.33-36
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• 2019

Mucosa-associated lymphoid tissue (MALT) lymphoma has specific clinical and pathologic features. The most common site MALT lymphomas is the stomach; however, it can also occur in other organs, such as the salivary glands. MALT lymphoma is rare, but its prognosis is good. A 32-year-old man visited Konyang university hospital with parotid mass. Superficial partial parotidectomy was performed to exclude lymphoid neoplasms. IgH gene rearrangement analysis of the surgical specimen led to the diagnosis of MALT lymphoma. The patient underwent esophagogastroduodenoscopy, positron emission tomography-computed tomography, and whole-body bone scan. Regional or distant metastasis was not observed on staging workup. The patient underwent postoperative radiation therapy, there has been no recurrence of MALT lymphoma to date. Here, we report this rare case of parotid MALT lymphoma that was treated with surgery and postoperative radiation therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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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.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.30-36
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• 2006

Purpose: It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. Materials and Methods: From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of $30.6{\sim}59.4 Gy$ (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. Results: When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorph isms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorph isms also affected the decrease of the WBC and platelet count during radiation therapy. Conclusion: Although the present sample size was too small for fully evaluating this hypothesis, this study suggests that Arg399Gln polymorph isms of the XRCC1 genes may be used as one of the predictors for acute complications of chemoradiation therapy in colorectal cancer patients.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.11a
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• pp.51-66
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• 2006

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.

• 한국약용작물학회:학술대회논문집
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• 2006.11a
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• pp.51-66
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• 2006

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.

• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.183-188
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• 2006

The field of cytochrome P450 pharmacogenomics has progressed rapidly during the past 25 years. Recently, conjugating enzymes including sulfotransferase, acetyltransferase, glucuronosyltransferase and glutathione transferase have been also extensively studied. All the major human drug-metabolizing P450 enzymes and some conjugating enzymes have been identified and cloned, and the major gene variants that cause inter-individual variability in drug response and are related to adverse drug reactions have been identified. This information now provides the basis for the use of predictive pharmacogenomics to yield drug therapies that are more efficient and safer. Today, we understand which drugs warrant dosing based on pharmacogenomics to improve drug treatment. It is anticipated that genotyping could be used to personalize drug treatment for vast numbers of subjects, decreasing the cost of drug treatment and increasing the efficacy of drugs and health in general. It is assumed that such personalized P450 gene-based treatment which is so-called tailor(order)-made drug therapy would be relevant for 10-20% of all drug therapy in the future.

• Journal of Sasang Constitutional Medicine
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• v.13 no.2
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• pp.177-181
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• 2001

Sasang Constitutional Medicine is based on the diversity of Human being and medically developed the response variation to diseases and medicines. The diversity is categorized as four from physiology, pathology, symptoms, to therapy. So that is related the difference of individual characteristics in Western Science. Single nucleotide polymorphism is the basic tool to research genetic polymorphisms. We researched the polymorphism site of MTHFR gene on 1p36.3, which is relatively reported the occlusive vascular disease. In the clinical research of brain infarction, the occurrence was different according to constitution. The 677C/T Polymorphism site of MTHFR was not significantly different in constitution group. But this research was the first trial about the single nucleotide polymorphism according to constitution. The more researchs of many genes are necessary to find the characteristics of constitution.

• Proceedings of the Korean Society for Bioinformatics Conference
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• 2000.11a
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• pp.74-82
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• 2000

Prostate cancer initially responds and regresses in response to androgen depletion therapy, but most human prostate cancers will eventually recur, and re-grow as an androgen independent tumor. Once these tumors become hormone refractory, they usually are incurable leading to death for the patient. Little is known about the molecular details of how prostate cancer cells regress following androgen ablation and which genes are involved in the androgen independent growth following the development of resistance to therapy. Such knowledge would reveal putative drug targets useful in the rational therapeutic design to prevent therapy resistance and control androgen independent growth. The application of genome scale technologies have permitted new insights into the molecular mechanisms associated with these processes. Specifically, we have applied functional genomics using high density cDNA microarray analysis for parallel gene expression analysis of prostate cancer in an experimental xenograft system during androgen withdrawal therapy, and following therapy resistance, The large amount of expression data generated posed a formidable bioinformatics challenge. A novel template based gene clustering algorithm was developed and applied to the data to discover the genes that respond to androgen ablation. The data show restoration of expression of androgen dependent genes in the recurrent tumors and other signaling genes. Together, the discovered genes appear to be involved in prostate cancer cell growth and therapy resistance in this system. We have also developed and applied tissue microarray (TMA) technology for high throughput molecular analysis of hundreds to thousands of clinical specimens simultaneously. TMA analysis was used for rapid clinical translation of candidate genes discovered by cDNA microarray analysis to determine their clinical utility as diagnostic, prognostic, and therapeutic targets. Finally, we have developed a bioinformatic approach to combine pharmacogenomic data on the efficacy and specificity of various drugs to target the discovered prostate cancer growth associated candidate genes in an attempt to improve current therapeutics.

• Biomedical Science Letters
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• v.18 no.1
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• pp.76-78
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• 2012

MMP3 (Matrix metalloproteinase-3) is an important gene in the development of cardiovascular and metabolic diseases. It is also reported that the genotype of MMP3 could be a factor for disease conditions. So, SNP analysis is a prerequisite to study MMP3 related diseases. However, statistical data or analytical reports of this gene in the Korean population is not available. We have employed PCR and ARMS technique to amplify the position of Lys45Glu which is located within chromosome 11q22.3 and exon 2. Genomic DNA were extracted from 201 people. We found that, 17 individuals had the wild homozygote type (W/W, 8%), 98 individuals had the SNP homozygote type (S/S, 49%), 86 had the heterozygote type (W/S, 43%). This study should facilitate research on the cause of cardiovascular diseases due to polymorphisms in the MMP3 gene and to develop further therapy at the genetic level.