• Radiation Oncology Journal
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• v.15 no.3
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• pp.187-195
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• 1997

Purpose : To analyze the involvement of apoptosis regulatory genes p53, $p21^{wart/cip1}$ bax and bcl-2 in induction of apoptosis by radiation in murine tumors. Materials and methods : The radiation-sensitive ovarian carcinoma OCa-1, and the radiation-resistant hepatocarcinorna HCa-I were used. Tumors, 8 mm in diameter, were irradiated with 25 Gy and at various times after irradiation, ranging from 1 to 48 h, were analyzed histologically for apoptosis and by western blot for alterations in the expression of these genes. The p53 status of the tumors were determined by the polymerase chain reaction-single strand conformation polymorphism assay. Results : Both tumors were positive for wild-type p53. Radiation inducesd apoptosis in OCa-1 but not in HCa-1. Apoptosis developed rapidly, peaked at 2 h after irradiation and returned to almost the background level at 48 h In OCa-1 radiation upregulated the expression of p53, $p21^{wart/cip1}$. and the bcl-2/bax ratio was decreased. In HCa-1 radiation increased the expression of both p53 and $p21^{wart/cip1}$, although the increase of the latter was small The bcl-2/bax ratio was greatly increased. In general the observed changes occurred within a few hours after irradiation, and either preceded or coincided with development of apoptosis Conclusions : The development of apoptosis required upregulation of both p53 and $p21^{wart/cip1}$ as well as a decrease in bcl-2/bax ratio. In contrast, an increase in bcl-2/bax ratio Prevented apoptosis in the presence of upregulated p53 and $p21^{wart/cip1}$ . These findings indentified the involvement of multiple oncogenes in apoptosis regulation in vivo and demonstrate the complexity that may be associated with the use of a single oncogene assessment for Predicting the outcome of cancer therapy with cytotoxic agents.

• Radiation Oncology Journal
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• v.17 no.2
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• pp.151-157
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• 1999

Purpose : By sequencing the Erpressed Sequence Tags of human 걸ermal papilla CDNA library, we identified a clone named K872 of which the expression decreased during differentiation of HL6O cell line. Materials and Methods : K872 plasmid DNA was isolated according to QIA plasmid extraction kit (Qiagen GmbH, Germany). The nucleotide sequencing was performed by Sanger's method with K872 plasmid DNA. The most updated GenBank EMBL necleic acid banks were searched through the internet by using BLAST (Basic Local Alignment Search Tools) program. Nothern bots were performed using RNA isolated from various human tissues and cancer cell lines. The gene expression of the fusion protein was achieved by His-Patch Thiofusicn expression system and the protein product was identified on SDS-PAGE. Results : K872 clone is 1006 nucleotides long, and has a coding region of 675 nucleotides and a 3' non-coding region of 280 nucleotides. The presumed open reading frame starting at the 5' terminus of K872 encodes 226 amino acids, including the initiation methionine residue. The amino acid sequence deduced from the open reading frame of K872 shares $70\%$, identity with that of rat glutathione 5-transferase kappa 1 (rGSTKl). The transcripts were expressed in a variety of human tissues and cancer cells. The levels of transcript were relatively high in those tissues such as heart, skeletal muscle, and peripheral blood leukocyte. It is noteworthy that K872 was found to be abundantly expressed in coloreetal cancer and melanoma cell lines. Conclusion : Homology search result suggests that K872 clone is the human homolog of the rGSTK1 which is known to be involved in the resistance of cytotoxic therapy. We propose that meticulous functional analysis should be followed to confirm that.

• Journal of Chest Surgery
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• v.37 no.8
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• pp.672-683
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• 2004

Background: The treatment results of the advanced lung carcinoma is not satisfactory with the present therapeutic modalities: surgical resection, anti-cancer chemotherapy, and radiotherapy or combination therapy. To predict the prognosis of the non-small-cell lung carcinoma, TNM classification has been was as the basic categorization; however, it has been not satisfactory. It is necessary to consider the causes and the prognosis of the lung carcinoma from another points of view rather the conventional methods. We intended to find out the relationship between the major apoptotic factor, p53 gene and the prognosis of the patient with lung carcinoma. Material and Method: Three hundreds and fifty-nine patients with lung carcinoma who underwent surgery were analysed. We observed p53 protein accumulated in the cellular nuclei. The p53 protein was detected by immuno-histo-chemical method. We collected information of the patient retrospectively. Result: p53 protein densities were observed in 40% in average as a whole. The protein density was 44 percent in man, 25 percent in woman, 49 percent in the squamous cell carcinoma, and 38 percent in the adenocarcinoma. There were significant correlations between the p53 protein density and the mortality in the squamous cell carcinoma (p=0.025), follow-up duration in TNM stage I group (p=0.010), and follow-up duration in the lobectomy patient group (p=0.043), and tumor cell differentiation (p=0.009). p53 protein densities were significantly different between the lobectomy and the pneumonectomy group (p=0.044). Conclusion: The authors found that p53 protein had some correlations with the prognosis of the lung cancer partially in some factors. We suggest the p53 protein density could be used as a marker of prognosis in the non-small-cell lung carcinoma.

• Korean Journal of Environmental Biology
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• v.27 no.1
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• pp.58-65
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• 2009

The chemopreventive effects of naringenin derived from citrus on tumor migration and the possible mechanisms involved in this protection were investigated in HT-1080 tumor cells. In this study, we found that naringenin reduced phorbol 12-myristate 13-acetate (PMA)-enhanced matrix metalloproteinases (MMP)-9 activation in a dose-dependant manner and further inhibited HT-1080 cell migration. In addition, naringenin suppressed PMA-enhanced expression of MMP-9 protein, mRNA and transcription activity levels through suppression of nuclear factor $\kappa$B (NF-$\kappa$B) activation and activator protein-1 (AP-1) translocation without changing tissue inhibitor of metalloproteinase (TIMP)-1 level. Therefore, our results suggested that the inhibitory effects of naringenin on MMP-9 activation, relation of tumor migration in vitro possibly involve mechanisms related to its ability to suppress PMA-enhanced MMP-9 gene and protein expression through NF-$\kappa$B activation and AP-1 translocation. Overall, naringenin may be a valuable anti-invasive drug candidate for cancer therapy.

• Journal of Life Science
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• v.16 no.2 s.75
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• pp.199-205
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• 2006

Peroxisome proliferator activated receptor (PPAR)-$\alpha$ of three PPAR subtypes ($-\alpha,\;-\beta/-\gamma,\;-\delta$), which are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors, plays a key role in lipoprotein and glucose homeostasis. A variation in the PPAR-a gene expression has been suggested to influence the development of metabolic syndrome through alterations in lipid concentrations. The aim of our study was to investigate the association between the PPAR-a and metabolic syndrome among South Korean. A total of 542 health screen examinees were enrolled in this study who were examined in Kosin University Gospel Hospital from December, 2004 to July, 2005. The height, weight, waist circumference, and systolic and diastolic blood pressure of the subjects were examined and fasting blood glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride were measured by-sampling in venous blood. The metabolic syndrome was defined as the presence of three or more of the following : waist circumference men ${\geq}90cm$, women ${\geq}80cm$, blood pressure ${\geq}130/85mmHg$, fasting glucose ${\geq}110mg/dL$, HDL cholesterol men <40 mg/dL, women <50 mg/dL, triglyceride ${\geq}150mg/dL$. The blood pressure, fasting glucose, HDL cholesterol, triglyceride were evaluated by using the criteria of NECP ATP III and waist circumference was assessed by using the criteria of WHO Asia-Western Pacific. And the author compared the frequency of the PPAR-$\alpha$ mutation of L162V ($C{\rightarrow}G$ variant in exon 5) in a sample of 542 subjects with and without the metabolic syndrome by polymerase chain reaction allele-specific oligonucleotide (PCR-ASO) method. One (0.2%) hetero-isotype among high risk of metabolic syndrome was identified. The values of waist circumference, body mass index and low density lipoprotein cholesterol of the mutant were 100 cm, 28.6 $kg/m^2$ and 120 mg/dL, respectively. Although the author failed to see significant association between the presence of the PPAR-$\alpha$ L162V polymorphism and metabolic syndrome, one PPAR-$\alpha$ L162V polymorphism in metabolic syndrome patients was found.

• Journal of Life Science
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• v.19 no.6
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• pp.735-743
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• 2009

The common word flavonoids is often used to classify a family of natural compounds, highly abundant in all higher plants, that have received significant therapeutic interest in recent years. Naringin is associated with a reduced risk of heart disease, neurodegenerative disease, cancer and other chronic diseases; however the molecular basis of this effect remains to be elucidated. Thus we attempted to elucidate the anti-allergic effect of Naringin in ovalbumin (OVA)-induced asthma model mice. The OVA-induced mice showed allergic reactions in the airways. These included an increase in the number of eosinophils in bronchoalveolar lavage (BAL) fluid, an increase in inflammatory cell infiltration into the lung around blood vessels and airways, airway luminal narrowing, and the development of airway hyper-responsiveness (AHR). The administration of Naringin before the last airway OVA challenge resulted in a significant inhibition of all asthmatic reactions. Accordingly, this study may provide evidence that Naringin plays a critical role in the amelioration of the pathogenetic process of asthma in mice. These findings provide new insight into the immunopharmacological role of Naringin in terms of its effects on asthma in mice.