• Toxicological Research
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• v.20 no.2
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• pp.109-116
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• 2004

For the safety evaluation of adenovirus-mediated gene transfer, we investigated differential gene expressions after transfecting adenoviral vector containing p16 tumor suppressor gene (Ad5CMV-p16) into human non-small cell lung cancer cells. In the previous study, we showed adenovirus-mediated $p16^{INK4a}$ gene transfer resulted in significant inhibition of cancer cell growth. We investigated gene expression changes after transfecting Ad5CMV-p16, Ad5CMV (null type, a mock vector) into A549 cells by using cDNA chip and oligonucleotide microarray chip (1200 genes) which carries genes related with signal transduction pathways, cell cycle regulations, oncogenes and tumor suppressor genes. We found that $p16^{INK4a}$ gene transfer down regulated 5 genes (cdc2, cyclin D3, cyclin B, cyclin E, cdk2) among 26 genes involved in cell cycle regulations. Compared with serum-free medium treated cells, Ad5CMV-p16 changed 27 gene expressions, two fold or more on oligonucleotide chip. In addition, Ad5CMV-p16 did not seem to increase the tumorigenicity-related gene expression in A549 cells. Further studies will be needed to investigate the effect of Ad5CMV-p16 on normal human cells and tissues for safety evaluation.

• Korean Journal of Medicinal Crop Science
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• v.14 no.2
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• pp.96-100
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• 2006

Regions of allelic loss on chromosomes in many tumors of human and some experimental animals are generally considered to harbor tumor-suppressor genes involved in tumorigenesis. Allelotype analyses have greatly improved our under-standing of the molecular mechanism of radiation lymphomagenesis. Previously, we and others found frequent loss of heterozygosity (LOH) on chromosomes 4, 11, 12, 16 and 19 in radiation-induced lymphomas from several $F_1$, hybrid mice. To examine possible contributions of individual tumor-suppressor genes to tumorigenesis in p53 heterozygous deficiency, we investigated the genome-wide distribution and status of LOH in radiation-induced lymphomas from $F_1$ mice with different p53 status. In this study, we found frequent LOH (more than 20%) on chromosomes 4 and 12 and on chromosomes 11, 12, 16 and 19 in radiation-induced lymphomas from $(STS/A{\times}MSM/Ms)F_1$ mice and $(STS/A{\times}MSM/Ms)F_1-p53^{KO/+}$ mice, respectively. Low incidences of LOH (10-20%) were also observed on chromosomes 11 in mice with wild-type p53, and chromosomes 1, 2, 9, 17 and X in p53 heterozygous-deficient mice. The frequency of LOH on chromosomes 9 and 11 increased in the $(STS/A{\times}MSM/Ms)F_1-p53^{KO/+}$ mice. Preferential losses of the STS-derived allele on chromosome 9 and wild-type p53 allele on chromosome 11 were also found in the p53 heterozygous-deficient mice. Thus, the putative tumor-suppressor gene regions responsible for lymphomagenesis might considerably differ due to the p53 status.

• Journal of Gastric Cancer
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• v.3 no.4
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• pp.214-220
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• 2003

Purpose: The aim of this study was to investigate the frequency of loss of heterozygosity and the microsatellite instability at multiple tumor suppressor gene loci in gastric adenocarcinomas. Materials and Methods: Loss of heterozygosity and the microsatellite instability at several tumor suppressor gene loci were analyzed in 29 primary gastric carcinomas by using microdissection and the polymerase chain reaction. Results: Twenty-three ($79\%$) of the 29 cases demonstrated loss of heterozygosity at one or more loci. The frequency of loss of heterozygosity at the p53 locus was the highest ($63\%$) and those at the VHL, APC, p16, Rb, MEN1, BRCA1, DPC4, 3p21, and 16p13 region were $41\%,\;36\%,\;19\%,\;29\%,\;33\%,\;26\%,\;21\%,\;32\%,\;and\;11\%$, respectively. Compared with histological type, loss of heterozygosity was more common in diffuse-type gastric cancer (P<0.01). Interestingly, 9 of 10 tumors with allelic deletion at the p53 locus showed loss of heterozygosity at other tumor suppressor gene loci. The microsatellite instability was also detected in 6 ($20\%$) of the 29 cases at one or more loci. Conclusion: These data suggest that frequent loss of heterozygosity and the microsatellite instability at multiple tumor suppressor genes might be required for the development and the progression of gastric carcinomas and that p53 allelic loss may be the most frequent event in the development of gastric carcinomas.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3539-3548
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• 2012

The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.98-114
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• 2002

The completion of the draft sequence of the human genome has provided us with a partial list of known and putative human genes, the total number of which is estimated between 30, 000 and 45, 000 (1, 2). These genes provide many potential targets for drugs, some of which may be useful in stopping the growth of cancers. The development of gene-targeting anticancer drugs could be greatly facilitated by the ability to narrow down the list of human genes to those that are necessary for the growth of tumor cells. (omitted)

• Nuclear Medicine and Molecular Imaging
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• v.40 no.5
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• pp.237-242
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• 2006

Knowledge of molecular mechanisms governing malignant transformation brings new opportunities for therapeutic intervention against cancer using novel approaches. One of them is gene therapy based on the transfer of genetic material to an organism with the aim of correcting a disease. The application of gene therapy to the cancer treatment has led to the development of new experimental approaches such as suicidal gene therapy, inhibition of oncogenes and restoration of tumor-suppressor genes. Suicidal gene therapy is based on the expression in tumor cells of a gene encoding an enzyme that converts a prodrug into a toxic product. Representative suicidal genes are Herpes simplex virus type 1 thymidine kinase (HSV1-tk) and cytosine deaminase (CD). Especially, physicians and scientists of nuclear medicine field take an interest In suicidal gene therapy because they can monitor the location and magnitude, and duration of expression of HSV1-tk and CD by PET scanner.

• Journal of Gastric Cancer
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• v.17 no.4
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• pp.363-373
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• 2017

Purpose: The aims of this study were to evaluate the expression of the large tumor suppressor (LATS) genes LATS1 and LATS2 by immunohistochemical staining of gastric cancer, and to evaluate the clinicopathological significance of LATS expression and its correlation with overall survival (OS). Materials and Methods: LATS1 and LATS2 expression in a tissue microarray was detected by immunohistochemistry, using 264 gastric cancer specimens surgically resected between July 2006 and December 2009. Results: Low expression of LATS1 was significantly associated with more advanced American Joint Committee on Cancer (AJCC) stage (P=0.001) and T stage (P=0.032), lymph node (LN) metastasis (P=0.040), perineural invasion (P=0.042), poor histologic grade (P=0.007), and diffuse-type histology by the Lauren classification (P=0.033). Low expression of LATS2 was significantly correlated with older age (${\geq}65$, P=0.027), more advanced AJCC stage (P=0.001) and T stage (P=0.001), LN metastasis (P=0.004), perineural invasion (P=0.004), poor histologic grade (P<0.001), and diffuse-type histology by the Lauren classification (P<0.001). Kaplan-Meier survival analysis revealed significantly poor OS rates in the groups with low LATS1 (P=0.037) and LATS2 (P=0.037) expression. Conclusions: Expression of LATS1 or LATS2 is a significant marker for a good prognosis in patients with gastric cancer.

• Journal of Oriental Neuropsychiatry
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• v.18 no.1
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• pp.95-110
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• 2007

Objective : The purpose of this study was to investigate molecular basis of neuroprotective effect in total ginsenosides. After H202 induced neurotoxicity, gene expression profiling of SH-SY5Y neuroblastoma cells treated by total ginsenosides is analyzed. Method : After SH-SY5Y cells were cultured, they were damaged by H202 induced oxidative stress. After twenty four hours, experimental group is treated by total ginsenosides and control group is treated by 0.9% saline. A high density cDNA microarray chip is used to analyze the gene expression profiling of SH-SY5Y cells. The Significance Analysis of Microarray method is used for identifying genes on a microarray. Results : 1. According to the results of microarray experiment, 17 genes were up-regulated, 38 genes were down-regulated. 2. Expression of OPHNl, KTANl, ATM, PRKCE, MAPKs genes associated with cell proliferation, neural growth, and the prevention of apoptosis were increased. 3. Change of EPX gene was the greatest among all genes. EPX gene associated with oxidative stress, and tumor suppressor gene ADAM11 were decreased. Conclusion : According to this study, molecular basis of neuroprotective effect of total ginsenosides is as followings: the increase of gene expression associated with cell proliferation, neuron growth, the prevention of apoptotsis and decrease of gene expression associated with oxidative stress and tumor suppressor.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.12
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• pp.5005-5006
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• 2015

Gastric cancer as one of the most common cancers worldwide has various genetic and environmental risk factors including Helicobacter pylori (H.pylori) infection. Recently, loss of a tumor suppressor gene named promyelocytic leukemia (PML) has been identified in gastric cancer. However, no mutation has been found in this gene in gastric cancer samples. Cag A H.pylori protein has been shown to exert post transcriptional regulation of some tumor suppressor genes. In order to assess such a mechanism for PML degradation, we performed in silico analyses to establish any interaction between PML and Cag A proteins. In silico interaction and docking studies showed that these two proteins may have stable interactions. In addition, we showed that imatinib kinase inhibitor can restore PML function by inhibition of casein kinase 2.

• Journal of Chest Surgery
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• v.42 no.2
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• pp.141-147
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• 2009

Background: We performed this study to identify the tumor suppressor genes located in the long arm of chromosome 21 in non-small cell lung cancer. Material and Method: The genes of USP25 in 21q11.2, NCAM2, ADAMTS1 in 21q21.2, and Claudin-8 (CLDN8), Claudin-17 (CLDN17) and TIAM1 in 21q22.1 were investigated for their gene expressions, genetic alterations and promoter methylation. Result: The expressions of CLDN8 and CLDN17 were significantly decreased in 7 (L132, H157, H358, H522, H1299, H1703 and HCC2108) of 13 cell lines, and the expression of ADAMTS1 was also significantly reduced in 6 cell lines (A549, SW900, H1299, H1373, H1703 and H1793). There were no genetic alterations by PCR-SSCP and cDNA cloning in the cell lines with a decreased gene. In the cell lines with a decreased gene expression, the mRNA expression was increased significantly with treatment of 5-Aza-CdR. Conclusion: These results suggest that the ADMTS1, CLDN8 and CLDN17 may act as tumor suppressor genes.