• Maxillofacial Plastic and Reconstructive Surgery
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• v.22 no.4
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• pp.373-382
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• 2000

Individual genetic susceptibilities to cancers may result from several factors including differences in xenobiotics metabolism to chemical carcinogens, DNA repair, altered oncogenes and suppressor genes, and environmental carcinogen exposures. Among them, genetic polymorphisms of metabolizing enzymes to chemical carcinogens have been recognized as a major important host factors in human cancers. They have two main types of enzymes: the phase I cytochrome P-450 mediating enzymes (CYPs) and phase II conjugating enzymes. The purpose of this study is to determine the frequencies of genotypes of phase I (CYP1A1 and CYP2E1) and phase II (NAT2) metabolizing enzymes in healthy control and head and neck cancer patients of Korean and to identify the relative high risk genotypes of these metabolizing enzymes to head and neck cancer in Korean. The author has analyzed 132 head and neck cancer patients and 113 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results were as following; 1. The frequencies of genotypes of CYP1A1, CYP2E1 and NAT2 in healthy control were as following; CYP1A1 exon 7 polymorphism; Ile/Ile: Ile/Val: Val/Val = 59.3%: 36.3%: 4.4% CYP2E1 Pst I polymorphism, C1/C1: C1/C2: C2/C2 = 61.1%: 32.1%: 6.2% NAT2 polymorphism; F/F: F/S: S/S = 43.4%: 48.7%: 8.0% 2. In analysis of phase I enzyme, Val/Val genotype in CYP1A1 exon 7 polymorphism and C2/C2 genotype in CYP2E1 Pst I polymorphism were associated with relative high risks to head and neck cancers (Odds' ratio: 2.09 and 1.37, respectively). 3. Among the genotypes of NAT2 enzyme polymorphism, S/S genotype of NAT2 enzyme had 1.03 times of relative risk to head and neck cancers. 4. In combined genotyping of CYP1A1, CYP2E1, and NAT2 enzymes polymorphisms, the patients with Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator had higher relative risks than the patients with each baseline of combined genotypes (Odds' ratio: 2.82, 1.98 and 2.1, respectively). These results suggest the combined genotypes of Val/Val and C1/C1, C2/C2 and fast acetylator, and Val/Val and fast acetylator were more susceptible to head and neck cancers in Korean. And genotyping of metabolizing enzymes could be useful for predicting individual susceptibility to head and neck cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7071-7076
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• 2015

Epidermal growth factor receptor (EGFR) is one of the targeted molecular markers in many cancers including lung malignancies. Gefitinib and erlotinib are two available therapeutics that act as specific inhibitors of tyrosine kinase (TK) domains. We performed a case-control study with formalin-fixed paraffin-embedded tissue blocks (FFPE) from tissue biopsies of 167 non-small cell lung carcinoma (NSCLC) patients and 167 healthy controls. The tissue biopsies were studied for mutations in exons 18-21 of the EGFR gene. This study was performed using PCR followed by DNA sequencing. We identified 63 mutations in 33 men and 30 women. Mutations were detected in exon 19 (delE746-A750, delE746-T751, delL747-E749, delL747-P753, delL747-T751) in 32 patients, exon 20 (S786I, T790M) in 16, and exon 21 (L858R) in 15. No mutations were observed in exon 18. The 63 patients with EFGR mutations were considered for upfront therapy with oral tyrosine kinase inhibitor (TKI) drugs and have responded well to therapy over the last 15 months. The control patients had no mutations in any of the exons studied. The advent of EGFR TKI therapy has provided a powerful new treatment modality for patients diagnosed with NSCLC. The study emphasizes the frequency of EGFR mutations in NSCLC patients and its role as an important predictive marker for response to oral TKI in the south Indian population.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.451-457
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• 2012

One decade early onset of the breast cancer in Iranian females was reported but the basis of the observed difference has remained unclear and difference in gene silencing by epigenetic processes is suggested. Hence, this study was sought to map the methylation status of estrogen receptor (ER) gene CpG islands and its impact on clinicopathological factors of triple negative and non-triple negative ductal cell carcinoma of the breast in Iranian females. Surgically resected formalin-fixed paraffin-embedded breast tissues from sixty Iranian women with confirmed invasive ductal carcinoma were assessed by methylation-specific PCR using primer sets encompassing some of the 29 CpGs across the ER gene CpG island. The estrogen and progesterone receptors, Her-$2^+$ overexpression, and nuclear accumulation of P53 were examined using immunohistochemistry (IHC). Methylated ER3, ER4, and ER5 were found in 41.7, 11.3, and 43.3% of the samples, respectively. Significantly higher methylation of ER4 was found in the tumors with nuclear accumulation of P53, and significantly higher methylation of ER5 was found in patients with lymph node involvement and tumor with bigger size or higher grades. Furthermore, significantly higher rate of ER5 methylation was found in patients with Her-$2^+$ tumors and in postmenopausal patients with $ER^-$, $PgR^-$, or $ER^-/PgR^-$ tumors. However, no significant difference in ERs methylation status was found between triple negative and non-triple negative tumors in pre- and postmenopausal patients. Findings revealed that aberrant hypermethylation of the ER-alpha gene frequently occurs in Iranian women with invasive ductal cell carcinoma of the breast. However, methylation of different CpG islands produced a diverse impact on the prognosis of breast cancer, and ER5 was found to be the most frequently methylated region in the Iranian women, and could serve as a marker of poor prognosis.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.1
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• pp.69-73
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• 2012

Cancer is a complex disease and the genetic susceptibility to it could be an outcome of the inherited difference in the capacity of xenobiotic metabolizing enzymes. Glutathione-S-transferases (GSTs) are phase II metabolizing enzymes whose various genotypes have been associated with increased risk of different types of cancer. Null mutations caused by the deletion of the entire gene result in the absence of the enzymatic activity and increase in the risk of developing cancer including chronic myeloid leukaemia (CML). In the present case-control study we evaluated the effect of null mutations in GSTM1 and GSTT1 genes on the risk of developing CML. The study included 75 CML patients (43 males and 32 females; age (mean ${\pm}$ S.D) $42.3{\pm}13.4$ years) and unrelated non-malignant controls (76 male and 48 females; age (mean ${\pm}$ S.D) $41.5{\pm}12.9$). The distribution of GSTM1 and GSTT1 genotypes in CML patients and controls was assessed by multiplex-PCR method. Logistic regression was used to assess the relationship between GSTM1 and GSTT1 genotypes and risk of CML. Chi-square test was used to evaluate the trend in modulating the risk to CML by one or more potential high risk genotype. Although GSTM1 null genotype frequency was higher in CML patients (41%) than in the controls (35%), it did not reached a statistical significance (OD = 1.32, 95% CI: 0.73-2.40; P value = 0.4295). The frequency of GSTT1 null genotypes was higher in the CML patients (36%) than in the controls (21%) and the difference was found to be statistically significant (OD = 2.12, 95% CI: 1.12-4.02; P value = 0.0308). This suggests that the presence of GSTT1genotype may have protective role against the CML. We found a statistically significant (OD = 3.09, 95% CI: 1.122-8.528; P value = 0.0472) interaction between the GSTM1 and GSTT1 null genotypes and thus individuals carrying null genotypes of both GSTM1 and GSTT1 genes are at elevated risk of CML.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4597-4606
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• 2012

Cholangiocarcinoma (CCA) is an uncommon adenocarcinoma which arises from the epithelial cells of the bile ducts. The aim of the study was to investigate the cytotoxicity, toxicity, and anticancer activity of a crude ethanolic extract of ginger (Zingiber officinale Roscoe) against CCA. Cytotoxic activity against a CCA cell line (CL-6) was assessed by calcein-AM and Hoechst 33342 assays and anti-oxidant activity was evaluated using the DPPH assay. Investigation of apoptotic activity was performed by DNA fragmentation assay and induction of genes that may be involved in the resistance of CCA to anticancer drugs (MDR1, MRP1, MRP2, and MRP3) was examined by real-time PCR. To investigate anti-CCA activity in vivo, a total of 80 OV and nitrosamine (OV/DMN)-induced CCA hamsters were fed with the ginger extract at doses of 1000, 3000, and 5000 mg/kg body weight daily or every alternate day for 30 days. Control groups consisting of 10 hamsters for each group were fed with 5-fluorouracil (positive control) or distilled water (untreated control). Median $IC_{50}$ (concentration that inhibits cell growth by 50%) values for cytotoxicity and anti-oxidant activities of the crude ethanolic extract of ginger were 10.95, 53.15, and $27.86{\mu}g/ml$, respectively. More than ten DNA fragments were visualized and up to 7-9 fold up-regulation of MDR1 and MRP3 genes was observed following exposure to the ethanolic extract of ginger. Acute and subacute toxicity tests indicated absence of any significant toxicity at the maximum dose of 5,000 mg/kg body weight given by intragastric gavage. The survival time and survival rate of the CCA-bearing hamsters were significantly prolonged compared to the control group (median of 54 vs 17 weeks). Results from these in vitro and in vivo studies thus indicate promising anticancer activity of the crude ethanolic extract of ginger against CCA with the absence of any significant toxicity. Moreover, MDR1 and MRP3 may be involved in conferring resistance of CCA to the ginger extract.

• Korean Journal of Ecology and Environment
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• v.50 no.2
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• pp.266-274
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• 2017

We surveyed the habitat use and food materials of the endangered Swan Goose (Anser cygnoides) during the wintering period at the Seocheon tidal flat. The bird wintered about six months from October 2014 to early April 2015 at the flat. They showed a remarkable change in choosing their feeding habitat and prey. They stayed entirely at sedge grass patches on Songrim tidal flat during the early wintering period (October), while after November they gradually moved to Janggu bay and used rice paddy fields as well as sedge patches on the tidal flats as their feeding site. The dietary analysis showed the sedge grass (Bolboschoenus sp., Cyperaceae) was the main dietary source during the entire wintering period. Interestingly, the proportion of Cyperaceae on feces decreased slightly over wintering time, while the proportion of Fabaceae increased relatively since November. These results suggest that the Swan Geese switched their habitat and food sources in response to the change of food availability. The Seocheon tidal flat area is the important wintering site for Swan Geese and sedge grass patches in the area need to be managed as the main feeding area for the wintering Swan Geese.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.5
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• pp.1873-1880
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• 2015

Background: A recent genome-wide association study (GWAS) on patients with chronic hepatitis C (CHC) treated with peginterferon and ribavirin (pegIFN-${\alpha}$/RBV) identified a single nucleotide polymorphism (SNP) on chromosome 19 (rs12979860) which was strongly associated with a sustained virological response (SVR). The aim of this study was twofold: to study the relationship between IL28B rs12979860 and sustained virological response (SVR) to pegIFN-${\alpha}$/RVB therapy among CHC patients and to detect the rs12979860 polymorphism by high resolution melting curve (HRM) assay as a simple, fast, sensitive, and inexpensive method. Materials and Methods: The study examined outcomes in 100 patients with chronic hepatitis C in 2 provinces of Iran from December 2011 to June 2013. Two methods were applied to detect IL28B polymorphisms: PCR-sequencing as a gold standard method and HRM as a simple, fast, sensitive, and inexpensive method. Results: The frequencies of IL28B rs12979860 CC, CT, and TT alleles in chronic hepatitis C genotype 1a patients were 10% (10/100), 35% (35/100), and 6% (6/100) and in genotype 3a were 13% (13/100), 31% (31/100), and 5% (5/100), respectively. In genotype 3a infected patients, rs12979860 (CC and CT alleles) and in genotype 1a infected patients (CC allele) were significantly associated with a sustained virological response (SVR). The SVR rates for CC, CT and TT (IL28B rs12979860) were 18%, 34% and 4%, respectively. Multiple logistic regression analysis identified two independent factors that were significantly associated with SVR: IL-28B genotype (rs 12979860 CC vs TT and CT; odds ratio [ORs], 7.86 and 4.084, respectively), and HCV subtype 1a (OR, 7.46). In the present study, an association between SVR rates and IL28B polymorphisms was observed. Conclusions: The HRM assay described herein is rapid, inexpensive, sensitive and accurate for detecting rs12979860 alleles in CHC patients. This method can be readily adopted by any molecular diagnostic laboratory with HRM capability and will be clinically beneficial in predicting treatment response in HCV genotype 1 and 3 infected patients. In addition, it was demonstrated that CC and CT alleles in HCV-3a and the CC allele in HCV-1a were significantly associated with response to pegIFN-${\alpha}$/RBV treatment. The present results may help identify subjects for whom the therapy might be successful.

• Journal of Acupuncture Research
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• v.20 no.6
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• pp.45-62
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• 2003

Objective: This study was designed to investigate effects of Nokyongsageunhwan and Nokyongsageunhwan aquapuncuture on body weight, body length, intellectual development Methods: We observed body weight, body length, intellectual development after feeding Nokyongsageunhwan and Nokyongsageunhwan aquapuncuture for thirty three days, and mRNA expressions of GHRF, Somatostatin, IGF-1, NPY were analyzed by RT-PCR method. Results: The results were summarized as follows. 1. Body length was significantly increased in Nokyongsageunhwan herbal acupuncture group compared to normal group and normal saline injection group on 4th week, 2. Lower part of hind leg length was significantly increased in Nokyongsageunhwan oral administration group compared to normal group on 3rd week, and it was significantly increased in Nokyongsageunhwan herbal acupuncture group and Nokyongsageunhwan oral administration group compared to that of normal group on 4th week. 3. As results of observing memory aquisition using Morris water maze system, there was significantly difference in Nokyongsageunhwan oral administration group compared to that of normal group on 4th week. 4. As results of observing retention using Morris water maze system, staying time was significantly increased in Nokyongsageunhwan herbal acupuncture group compared to that of normal group. 5. The somatostatin mRNA expression in the hypothalamus was significantly decreased in Nokyongsageunhwan oral administration group compared to that of normal group. 6. The IGF-1 mRNA expression in the hypothalamus is significantly increased in Nokyongsageunhwan herbal acupuncture group and Nokyongsageunhwan oral administration group compared to that of normal group. 7. The NPY mRNA expression in the hypothalamus was significantly increased in Nokyongsageunhwan oral administration group compared to that of normal group, and it was increased in Nokyongsageunhwan herbal acupuncture group compared to that of normal group, but there was no significant difference. Conclusions: According to the above results, it appears that Nokyongsageunhwan oral administration and Nokyongsageunhwan herbal acupuncture on acupoint GB34 and GB39 showed effects on the growth and the intellectual development of rats.

• The Journal of Pediatrics of Korean Medicine
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• v.32 no.3
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• pp.1-15
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• 2018

Objectives Alismatis Rhizoma has been known to suppress inflammation and allergic reaction. However, the cellular target of Alismatis Rhizoma and its mechanism of action remain unclear. This study was designed to examine the effect of Alismatis Rhizoma extract (ALC) on the RBL-2H3 mast cells in vitro and on the OVA/alum sensitized mice ex vivo. Methods In the study, RBL-2H3 mast cells were cultured in minimal essential medium (MEM) for 24 hours, and treated separately with cyclosporin A and varying doses of ALC, and then stimulated with Phorbol 12-myristate 13-acetate (PMA) (50 ng/ml) and Ionomycin ($0.5{\mu}M$). The levels of IL-13, IL-4 were measured by ELISA analysis. The mRNA levels of IL-4, IL-5, IL-6, IL-13, GM-CSF, $TNF-{\alpha}$ were analyzed with Real-time PCR. Also, manifestations of MAPKs transcription factors and $NF-{\kappa}B$ p65 translocation were analyzed by western blotting in vitro. Subsequently, for ex vivo experiment, we induced allergic inflammation on Balb/c mice by OVA/alum and administered ALC orally. And we measured serum OVA-specific IgE level and IL-4, IL-13 in the splenocyte culture supernatant by ELISA analysis. Results ALC was shown to suppress mRNA expression of IL-4, IL-5, IL-6, IL-13, GM-CSF, $TNF-{\alpha}$, and to inhibit the IL-13, IL-4 production. Also ALC reduced an activation of mast cells specific signal MAPKs transcription factors and $NF-{\kappa}B$ p65 from the western blot analysis in in vitro experiment. In ex vivo, ALC oral adminstration decreased the level of OVA-specific IgE in serum, and IL-4, IL-13 in the splenocyte culture supernatant. Conclusions ALC is shown to reduce inflammation and allergic response by suppressing Th2 cytokines through the regulation of transcription factors MAPKs and $NF-{\kappa}B$ p65 in mast cells. Administration of ALC suppressed OVA-specific IgE in ovalbumin allergy model through the inhibition of Th2 cytokine. In conclusion, ALC can be considered as an effective treatment for allergic diseases such as atopic dermatitis.

• Tuberculosis and Respiratory Diseases
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• v.62 no.3
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• pp.197-202
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• 2007

Background: Cigarette smoking is an important risk factor for chronic bronchitis and COPD. Airway epithelial cells exposed to cigarette smoke components such as nicotine, cotinine and benzopyrene can generate reactive oxygen species (ROS) and be subject to oxidative stress. This oxidative stress can induce the inflammatory response in the lung by the oxidant itself or by the release of proinflammatory cytokines. It has been reported that nicotine stimulates ROS, which are associated with NF-${\kappa}B$. Methods: Beas2B cells were treated with nicotine, cotinine and benzopyrene. RT PCR was used to measure the expression of several antioxidant factors using the total RNA from the Beas2B cells. The level of superoxide dismutase(CuZnSOD), thioredoxin, glutathione reductase expression was examined. Results: 0.5 to 4 hours after the benzopyrene, nicotine and cotinine theatments, the level of thioredoxin and glutathione reductase expression decreased. Longer exposure to these compounds for 24 to 72 hours inhibited the expression of most of these antioxidant factors. Conclusion: During exposure to smoke compounds, thioredoxin and glutathione reductase are the key antioxidant factors induced sensitively between 0.5 and 4 hours but the levels these antioxidants decrease between 24 hour and 72hours.