• Journal of Chest Surgery
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• v.36 no.1
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• pp.7-14
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• 2003

Cyclin I plays a pivotal role in the regulation of G1-S transition and could consequently be a deregulated molecule in tumors. The activity of the cdk2-cyclin E complex is increased by degradation of cdk inhibitor p27kip1. Little is known about the expression and prognostic significance of cyclin E and p27 in non-small cell lung cancer(NSCLC). Material and Method: The expression of cyclin E and p27 in eighty-one cases of resected stage I NSCLC tissues and its relation to major clinico-pathological factors, including histology, differentiation, size of tumor, pleural invasion and survival rate were studied and analyzed. Immunohistochemical analysis with monoclonal antibodies specific for cyclin E and p27 were performed by ABC method. Result: Expression rates of cyclin E and p27 in stage I NSCLC tissues were 29.6% and 28.4% respectively. Cyclin E was expressed higher in cases of pleural invasion(p=0.04), and p27 was expressed higher in diameter of tumor less than 3cm(p=0.015). The 5-years survival rate was lower in cases of Positive expression of cyclin E than in cases of negative expression of cyclin E(44.4% vs 68.2%, p=0.015), and the 5-years survival rate was 72.2% in positive expression of p27 and 56.2% in negative expression of p27(p=0.09). The 5-years survival rate was higher in negative expression of cyclin E and positive expression of p27 than in cases of positive expression of cyclin I and negative expression of p27 (73.5% vs 36.3%, p=0.0029). In multivariate analysis, expression of cyclin I was an unfavorable prognostic factor(RR=3.578, p=0.006) and p27 was a favorable prognostic factor(RR=0.183, p=0.019) independently. Conclusion: Cyclin E and p27 may play a pivotal role for the biological behavior of stage I NSCLC, so that the expressions of cyclin I and p27 nay be new prognostic markers.

• Korean Journal of Ecology and Environment
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• v.50 no.1
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• pp.137-147
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• 2017

The identity of toxin producers remains only hypothesis unless there were identified by strain isolation and analytical confirmation of both the cyanotoxin production and the genetic identity of the monoculture. The purposes of this study were to identify a morphologic and phylogenetic classification in Aphanizomenon flos-aquae strains isolated from the Nakdong River and to investigate the potential ability of the strains to produce toxins such as saxitoxin and cylindrospermopsin using target genes. The 16S rRNA and sxtA, sxtI, cyrA, cyrJ genes were analyzed on two strains (DGUC001, DGUC003) isolated from the Nakdong River. Morphological features of the strains were observed a shape of aggregated trichomes in parallel fascicles which can reach up to macroscopic size and a hyaline terminal cell without aerotope. In addition, the 16S rRNA phylogenetic analyses showed that the strains were identified as the same species with high genetic similarity of 98.4% and grouped within a monospecific andsupported cluster I of Aphanizomenon flos-aquae selected from GenBank of the NCBI. The cyrA and cyrJ genes encoding for the cylindrospermopsin-biosynthesis were not detected in the present study. The sxtA gene was in detected both the two strains, whereas the sxtI gene which had been suggested as a suitable molecular marker to detect saxitoxin-producing cyanobacteria was not found both the strains. Thus, the two strains isolated from Nakdong River were identified as the same species of Aphanizomenon flos-aquae Ralfs ex Bornet et Flahault 1888, the two strains were confirmed as potential non-producing strains of the saxitoxin and cylindrospermopsin.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.107-116
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• 2002

Background: Matrix metalloproteinases(MMP) are essential enzymes for tumor invasion and metastasis. Among the MMP family, elevated MMP-9 and stromelysin-3(STR-3) expression have been reported to be poor prognostic factors in lung cancer patients. To evaluate the possibility of a molecular diagnosis of lung cancer using peripheral blood, the mRNA expression level of MMP-9 and STR-3 was measured using a reverse transcriptase-polymerase chain reaction (RT-PCR) in patients with lung cancer. Methods : Ninety six patients(44 patients with lung cancer, 19 pulmonary infection, and 33 control) were included. To detect MMP-9 and STR-3 mRNA expression, RT-PCR was performed in peripheral blood mononuclear cells. ELISA was also used to measure the serum level of MMP-9. Results : MMP-9 was expressed more frequently in patients with a pulmonary infection(18/19, 94.7%) compared to lung cancer patients(26/44, 59.1%) or the controls (23/33, 69.7%) (p=0.018). On the other hand, STR-3 expression was observed more frequently in patients with lung cancer(37/44, 84.1%) compared to the lung infection patients(8/19, 42.1%) or control(20/33, 60.6%) (p=0.003). Among the lung cancer patients, MMP-9 was expressed more frequently when a tumor invaded the lymph nodes(17/24, 70.8%) compared to when a tumor did not(3/13, 23.1%) (p=0.005). The MMP-9 and STR-3 expression levels had no relationship with age, sex, tumor size, distant metastasis, or tumor histology. The serum MMP-9 concentration was not higher in lung cancer patients compared to patients with a pulmonary infection or the control subjects. Conclusion : STR-3 may be used as a diagnostic marker in the peripheral blood of lung cancer patients using RT-PCR. Further studies to evaluate the clinical significance of elevated STR-3 expression in lung cancer patients is recommended.

• Journal of Gastric Cancer
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• v.6 no.4
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• pp.227-236
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• 2006

Purpose: Methylation of gene regulatory elements plays an important role in gene inactivation without genetic alteration. Gastric cancer is one of the tumors that exhibit a high frequency of CpG island hypermethylation. The purpose of this study was to investigate the occurrence of CpG island hypermethylation in gastric carcinoma in relation to H. pylori infection, CIMP and clincopathologic variables. Materials and Methods: We investigated the promoter methylation Status of six genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin) and CIMP in 36 gastric carcinoma tissues as well as in nontumor tissues. CIMP status was investigated by examining the methylation status of MINT 1, 2, 12, 25 and 31. The methylation status of the promoter was examined by methylation-specific PCR (MSP) and H. pylori infection was examined by histological diagnosis after staining with Warthin-Starry silver. Results: Among the 36 gastric carcinoma tissues, DNA hypermethylation was detected in the following frequencies: 14 (38.9%) for p14, 13 (36.1%) for p16, 8 (22.2%) for MGMT, 10 (27.8%) for COX-2, 21 (58.3%) for E-cadherin, and 6 (16.7%) for hMLH1. The frequencies for MINT1 and MINT25 hypermethylation were significantly higher in tumor tissues than in nontumor tissues. 16 (44.4%) of the 36 gastric carcinoma tissues were positive for the CIMP CIMP-H tumors were associated with older patients and larger tumor size than CIMP-L tumors. We found a significant association between the presence of the CIMP and hypermethylation of p16. Hypermethylation of p16 and MINT2 were significantly different when compared by age. MINT1 gene methylation was significantly associated with H. pylori infection (P=0.004). Conclusion: Our results suggest that aberrant hypermethylation of multiple tumor related genes (hMLH1, p16, p14, COX-2, MGMT, E-cadherin, MINT1, 2, 12, 25, 31) occurs frequently in gastric carcinoma tissues. The hypermethylation of MINT1 was significantly higher in the tumor tissues and was associated with H. pylori infection.

• Development and Reproduction
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• v.10 no.4
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• pp.227-238
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• 2006

Genomic DNAs(gDNAs) were isolated from the venus clam(Gomphina aequilatera) from Samcheok(venus clam from Samcheok; VCS) and Wonsan(venus clam from Wonsan; VCW) located in the East Sea of the Korean Peninsula. The amplified products were generated by agarose gel electrophoresis(AGE) with oligonucleotides primer, detected by staining with ethidium bromide and viewed by ultraviolet ray. The seven arbitrarily selected primers BION-21, BION-23, BION-25, BION-27, BION-29, BION-31 and BION-33 generated the shared loci, polymorphic, and specific loci, with the molecular sizes ranging from 150 bp to 2,400 bp. In this study, 147 polymorphic loci(147/954 loci, 15.41%) in VCS population and 274(274/996 loci, 27.51%) in VCW population were generated with seven primers. These results suggest the genetic variation in VCW population is higher than in VCS population. Especially, the 700 bp bands generated by the primer BION-21 were identified commonly in two Gomphina populations, which identified populations and/or species. This specific primer was found to be useful in the identification of individuals and/or population, resulting from the different DNA polymorphism among individuals/species/population. Two Gomphina populations between the individual SAMCHEOK no. 03 and WONSAN no. 22 showed the longest genetic distance(0.696) in comparison with other individuals used. The complete linkage cluster analysis indicating three genetic groupings and dendrogram revealed close relationships among individual identities within two geographical populations of venus clam(G. aequilatera) from the Samcheok and Wonsan. The intra-species classification and clustering analyses inferred from molecular markers supported the traditional taxonomy of the species based on morphological characters such as shell size, shape and color. Accordingly, as mentioned above, RAPD analysis showed that VCS population was more or less separated from VCW population.

• Radiation Oncology Journal
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• v.22 no.4
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• pp.288-297
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• 2004

Puporse: The aims of this study were to evaluate the change of $[^18F]fluoromisonidazole$($[^18F]FMISO$) uptake in C3H mouse squamous cell carcinoma-VII (SCC-VII) treated with mild hyperthermia ($42^{circ}C$) and nicotinamide and to assess the biodistribution of the markers in normal tissues under similar conditions. Methods and Materials: $[^18F]FMISO$ was producedby our hospital. Female C3H mice with a C3H SCC-VII tumor grown on their extremities were used. Tumors were size matched. Non-anaesthetized, tumor-bearing mice underwent control or mild hyperthermia at $42^{circ}C$ for 60 min with nicotinamide (50 mg/kg i.p. injected) and were examined by gamma counter, autoradiography and animal PET scan 3 hours after tracer i.v. injected with breathing room air, The biodistribution of these agents were obtained at 3 h after $[^18F]FMISO$ injection. Blood, tumor, muscle, heart, lung, liver, kidney, brain, bone, spleen, and intestine were removed, counted for radioactivity and weighed. The tumor and liver were frozen and cut with a cryomicrotome into 10- um sections. The spatial distribution of radioactivity from the tissue sections was determined with digital autoradiography. Results: The mild hyperthermia with nicotinamide treatment had only slight effects on the biodistribution of either marker in normal tissues. We observed that the whole tumor radioactivity uptake ratios were higher in the control mice than in the mild hyperthermia with nicotinamide treated mice for $[^18F]FMISO$ ($1.56{\pm}1.03$ vs. $0.67{\pm}0.30$; p=0.063). In addition, autoradiography and animal PET scan demonstrated that the area and intensity of $[^18F]FMISO$ uptake was significantly decreased. Conclusion: Mild hyperthermla and nicotinamide significantly improved tumor hypoxia using $[^18F]FMISO$ and this uptake reflected tumor hypoxic status.

• Journal of Nutrition and Health
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• v.44 no.1
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• pp.5-15
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• 2011

Although iron is an essential mineral, excess iron intake during pregnancy may increase oxidative stress in tissues. This study was conducted to investigate the effects of iron overload during pregnancy on iron status and oxidative stress in maternal rats. Ten week-old female Sprague-Dawley rats were mated with male rats. Non-pregnant (control) and pregnant rats were fed diets containing normal Fe (35 mg/kg diet), high Fe (350 mg/kg diet), or excess Fe (1,050 mg/kg diet) during pregnancy. Rats were sacrificed on pregnancy day 19. No significant difference in weight gain, diet intake, or litter size was observed according to iron intake levels. Furthermore, serum iron, hemoglobin, and hematocrit were not different among the rats administered the three levels of Fe both in the control and pregnant groups. However, the iron levels were lower in pregnant rats than those in the control. The liver and spleen iron contents increased significantly in the excess Fe group. An increase in liver ferritin levels with increasing iron intake was observed. Protein carbonyl content, as a marker of oxidative stress, increased significantly in liver with increasing iron intake but not malondialdehyde. Glutathione peroxidase activity in the liver of pregnant rats fed excess iron decreased significantly. Bcl-2 protein expression in the liver declined remarkably with increasing maternal iron intake in pregnant rats. Taken together, iron overload during pregnancy had little effect on hematology. However, the deposits of iron in the liver and the decline in antioxidant enzyme activity implied increased oxidative stress in tissues of the excess Fe group. These results suggest that excess iron intake during pregnancy increases oxidative stress in maternal tissues and may also affect fetal tissues.

• Tuberculosis and Respiratory Diseases
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• v.44 no.4
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• pp.785-795
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• 1997

Background : Tumor markers have been used in diagnosis, predicting the extent of disease, monitoring recurrence after therapy and prediction of prognosis. But the utility of markers in lung cancer has been limited by low sensitivity and specificity. TPA-M is recently developed marker using combined monoclonal antibody of Cytokeratin 8, 18, and 19. This study was conducted to evaluate the efficacy of new tumor marker, TPA-M by comparing the estabilished markers SCC, CEA, Cyfra21-1 in lung cancer. Method : An immunoradiometric assay of serum CEA, sec, Cyfra21-1, and TPA-M was performed in 49 pathologically confirmed lung cancer patients who visited Keimyung University Hospital from April 1996 to August 1996, and 29 benign lung diseases. Commercially available kits, Ab bead CEA (Eiken) to CEA, SCC RIA BEAD (DAINABOT) to SCC, CA2H (TFB) to Cyfra2H. and TPA-M (DAIICHI) to TPA-M were used for this study. Results : The mean serum values of lung cancer group and control group were $10.05{\pm}38.39{\mu}/L$, $1.59{\pm}0.94{\mu}/L$ in CEA, $3.04{\pm}5.79{\mu}/L$, $1.58{\pm}2.85{\mu}/L$ in SCC, $8.27{\pm}11.96{\mu}/L$, $1.77{\pm}2.72{\mu}/L$ in Cyfra21-1, and $132.02{\pm}209.35\;U/L$, $45.86{\pm}75.86\;U/L$ in TPA-M respectively. Serum values of Cyfra21-1 and TPA-M in lung cancer group were higher than control group (p<0.05). Using cutoff value recommended by the manufactures, that is $2.5{\mu}/L$ in CEA, $3.0{\mu}/L$ in Cyfra21-1, 70.0 U/L in TPA-M, and $2.0{\mu}/L$ in SCC, sensitivity and specificity of lung cancer were 33.3%, 78.6% in CEA, 50.0%, 89.7% in Cyfra21-1, 52.3%, 89.7% in TPA-M, 23.8%, 89.3% in SCC. Sensitivity and specificity of nonsmall cell lung cancer were 36.1%, 78.1% in CEA, 50.1%, 89.7% in Cyfra21-1, 53.1%, 89.7% in TPA-M, 33.8%, 89.3% in SCC. Sensitivity and specificity of small cell lung cancer were 25.0%, 78.5% in CEA, 50.0%, 89.6% in Cyfra21-1, 50.0%, 89.6% in TPA-M, 0%, 89.2% in SCC. Cutoff value according to ROC(Receiver operating characteristics) curve was $1.25{\mu}/L$ in CEA, $1.5{\mu}/L$ in Cyfra2-1, 35 U/L in TPA-M, $0.6{\mu}/L$ in SCC. With this cutoff value, sensitivity, specificity, accuracy and kappa index of Cyfra21-1 and TPA-M were better than CEA and SCC. SCC only was related with statistic significance to TNM stages, dividing to operable stages(TNM stage I to IIIA) and inoperable stages (IIIB and IV) (p<0.05). But no tumor markers showed any correlation with significance with tumor size(p>0.05). Conclusion : Serum TPA-M and Cyfra21-1 shows higher sensitivity and specificity than CEA and SCC in overall lung cancer and nonsmall cell lung cancer those were confirmed pathologically. SCC has higher specificity in nonsmall cell lung cancer. And the level of serum sec are signiticantly related with TNM staging.

• Journal of Chest Surgery
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• v.39 no.1 s.258
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• pp.1-11
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• 2006

Background: CD44 is a glycoprotein on the cell surface which is involved in the cell-to-cell and cell-to-matrix interaction. The standard form, CD44s and multiple isoforms are determined by alternative splicing of 10 exons. Recent studies have suggested that CD44 may help invasion and metastasis of various epithelial tumors as well as activation of Iymphocytes and monocytes. The expression pattern of CD44 can be different according to tumor types. The author studied the expression pattern of CD44s and one of its variants, CD44v6 in non-small cell lung carcinomas (NSCLC) to find their implications on clinicopathologic aspects, including the survival of the patients. Material and Method: A total of 89 primary NSCLSs (48 squamous cell carcinomas, 33 adenocarcinomas, and 8 undifferentiated large cell carcinomas) were retrieved during the years between 1985 to 1994. The immunohisto chemistry was done by using monoclonal antibodies and the CD44 expression for angiogenesis was evaluated by counting the number of tumor microvessels. Result: Seventy-one (79.8$\%$) and 64 (71 .9$\%$) among 89 NSCLSs revealed the expression of CD44s and CD44v6, respectively. The expression of CD44s was well correlated with that of CD44v6 (r=0.710, p < 0.0001). The expression of CD44s and CD44v6 was associated with the histopathologic type of the NSCLCs, and squamous cell carcinoma was the type that showed the highest expression of CD44s and CD44v6 (p < 0.0001). Microvessel count was the highest in adenocarcinomas (113.6$\pm$69.7 on 200-fold magnification and 54.8$\pm$41.1 on 400-fold magnification) and correlated with the tumor size of TNM system (r=0.217, p=0.043) and CD44s expression (r=0.218, p=0.040). In adenocarcinoma, the patients with higher CD44s expression survived shorter than those with lower CD44s expression (p=0.0194) but there was no statistical significance on multivariate analysis(p=0.3298). Conclusion: The expression of both CD44s and CD44v6 may be associated with the squamous differentiation in non-small cell lung carcinomas. The relationship of CD44s expression with micro-vessel density of the tumor suggests an involvement of CD44s in tumor angiogenesis, which in turn would help tumor growth.