• The Journal of the Korean bone and joint tumor society
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• v.11 no.2
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• pp.118-125
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• 2005

Purpose: The expression of apoptosis-related genes, such as survivin, bcl-2, and bax has been examined in the human osteosarcoma and then evaluated the correlation with clinical data of patients. Materials and Methods: Fifty human osteosarcoma specimens were established from incisional biopsy and examination of survivin, bcl-2, and bax by immunohistochemical study was performed. We investigated the correlation of survivin, bcl-2, bax and their two or three combined expressions with clinical data including the response of chemotherapy, local recurrence, distance metastasis, and oncologic outcome. Results: Survivin was showed in 26 cases (52%), bcl-2 in 23 cases (46%), and bax in 21 cases (42%) osteosarcoma. And coexpression of survivin and bcl-2 was showed in 19 cases (38%), survivin and bax in 13 cases (26%), bcl-2 and bax in 8 cases (16%), and all three expression was showed in 8 cases (16%). There was no correlation between their apoptosis related gene and histologic difference, the presence of local recurrence and distant metastasis. Whereas neoadjuvant chemotherapy response correlated with bcl-2 expression (P=0.04), and survivin and bcl-2 coexpression (P=0.044) with poor chemoresponse. The rate of died of disease was correlated with bcl-2 (P=0.001), survivin and bcl-2 coexpression (P=0.027) with bad outcome. Survival curves of bcl-2 (P=0.0075), survivin and bcl-2 (P=0.0012) was showed negative correlation in the Kaplan-Meier method. Conclusion: The apoptosis related gene expression was relatively high in osteosarcoma, bcl-2 expression was correlated with poor chemotherapy response and poor survival rate, but survivin was correlated with this oncologic outcome only in the bcl-2 coexpression. The examination of immunohistochemical stain of apoptosis related gene in osteosarcoma could be helpful in the judgment of osteosarcoma prognosis.

• Clinical and Experimental Pediatrics
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• v.45 no.4
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• pp.482-488
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• 2002

Purpose : We performed this study to evaluate the diagnostic usefulness of endoscopic finding of nodular gastritis, CLO and HpKit test for H. pylori infection in children. Methods : Gastroduodenal endoscopy and mucosal biopsy were performed on 212 children who visited our hospital between Jul. 1999 and May 2000 due to abdominal pain. We performed CLO and HpKit test for H. pylori with the time interval of 15, 30 minutes, 1, 2, 3, 24, 48, 72, 96, 120 and 144 hours. Histological examination of H. pylori was made by H-E or Alcian yellow stain with biopsy specimens. Sensitivity, specificity, positive predictive and negative predictive value of nodular gastritis, CLO and HpKit test were calculated from the analysis of above data. Results : Sensitivity and specificity of 3 hour-CLO test was 68.4% and 100% respectively. Sensitivity and specificity of 3 hour-HpKit test was 65.8% and 100% respectively. No significant difference in sensitivity and specificity was found between in 3 hour-CLO and HpKit test(P>0.05). Sensitivity of CLO test increased as time lapsed, but corresponding specificity did not decrease as time lapsed(sensitivity and specificity at 144 hours : 89.5% and 94.8% respectively). However, sensitivity of HpKit test increased as time lapsed, but specificity markedly decreased. Sensitivity and specificity of the nodular gastritis was 78.9% and 93.7% respectively. Conclusion : Both CLO and HpKit test have relatively low sensitivity and specificity for the detection of H. pylori in 3 hours of testing in children. The endoscopic finding of nodular gastritis is another good standard in the diagnosis of H. pylori infection in children.

• Korean Journal of Food Science and Technology
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• v.37 no.6
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• pp.989-996
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• 2005

Ultraviolet (UV) induces photo aging, erythema, sunburn, photo-toxicity, photo-allergy, and skin tumor, To investigate photo-protective effects of AmorePacific Beauty-03 (APB-03; mixture of red ginseng extract powder and soybean extract powder) on UV-induced damaged skins, 40 SKH hairless female mice were orally administered APB-03 or saline five times a week and irradiated with UV three times per week far up to 12 weeks. Visible skin changes and skin damage in dermis and epidermis by replica image analysis and histological analysis. In APB-03-treated group, better skin, negative replica appearance and less wrinkle formation were observed compared to the UV control group. These results demonstrate oral administration of APB-03 have photo-protective effects on UV-damaged hairless mouse skin.

• Tuberculosis and Respiratory Diseases
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• v.50 no.5
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• pp.599-606
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• 2001

Background : Since the advent of AIDS, tuberculosis has become a major public health problem in the western society. Therefore, it is essential that pulmonary tuberculosis be rapidly diagnosed. Light microscopic detection of acid-fast organisms in sputum has traditionally been used for rapidly diagnosing tuberculosis. However positive smears are only observed in about one-half to three-quarters of cases. Studies using PCR for diagnosing pulmonary tuberculosis disclosed several shortcomings suggesting an inability to distinguish between active and treated or inactive tuberculosis. In this study, the clinical significance of a PCR-based rapid technique for detecting Mycobacterium tuberculosis DNA in peripheral blood was investigated. Materials and Methods : From July 1, 1998 through to August 30, 1999, 59 patients with presumed tuberculosis, who had no previous history of anti-tuberculosis medication use within one year prior to this study were recruited and followed up for more than 3 months. AFB stain and culture in the sputum and/or pleural fluids and biopsies when needed were performed. Blood samples from each of the 59 patients were obtained in order to identify Mycobacterium Tuberculosis DNA by a PCR test. Results : 1) Forty five out of 59 patients had a final diagnosis of tuberculosis ; Twenty eight were confirmed as having active pulmonary tuberculosis by culture or biopsy. Four were clinically diagnosed with pulmonary tuberculosis. The other 13 patients were diagnosed as having tuberculous pleurisy (9) and extrapulmonary tuberculosis (4). 2) Fourteen patients showed a positive blood PCR test. The PCR assay correctly identified active tuberculosis in 13 out of 14 patients. The overall sensitivity and specificity of this blood peR assay for diagnosing tuberculosis were 29% and 93%, respectively. The positive predictive value was 93%, the negative predictive value was 29% and the diagnostic accuracy was 44%.3) Six out of 14(43%) patients with blood PCR positive tuberculosis were immunologically compromised hosts. 4) A simple chest radiograph in blood PCR positive tuberculosis patients showed variable and inconsistent findings. Conclusion : A peripheral blood PCR assay for Mycobacterium tuberculosis is not recommended as a screening method for diagnosing active tuberculosis. However, it was suggested that the blood PCR assay could contribute to an early diagnostic rate due to its high positive predictive value.

• Annals of Clinical Microbiology
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• v.18 no.2
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• pp.37-43
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• 2015

Background: Tuberculosis is globally the most important cause of death from single pathogen. Rapid and accurate identification of mycobacteria is essential for the control of tuberculosis. We evaluated a fluorescence in situ hybridization (FISH) method using peptide nucleic acid (PNA) probes for the differentiation of Mycobacterium tuberculosis complex (MTB) and nontuberculous mycobacteria (NTM) in direct smears of sputum specimens. Methods: The cross-reactivity of MTB- and NTM-specific PNA probes was examined with reference strains of M. tuberculosis ATCC 13950, Mycobacterium kansasii ATCC 12479, Mycobacterium fortuitum ATCC 6841, several clinical isolates of mycobacteria (Mycobacterium abscessus, Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium gordonae and Mycobacterium chelonae), and 11 frequently isolated respiratory bacterial species other than mycobacteria. A series of 128 sputa (89 MTB culture positive, 29 NTM culture positive, and 10 under treatment culture negative) with grades of trace to 4+ were used to evaluate the performance of the method. Results: The MTB- and NTM-specific PNA probes showed specific reactions with the reference strains of MTB and M. kansasii and clinical isolates of mycobacteria except M. fortuitum ATCC 6841, and no cross-reactivity with other tested bacteria. The PNA probe-based FISH assay for detection of MTB had a sensitivity and specificity of 100%, respectively. The sensitivity and specificity of the NTM-specific PNA probe was 100%. The smear grades of the PNA FISH test were same as with those of the fluorescence AFB stain in 2+ or higher grade. Conclusion: Detection and differentiation based on PNA FISH is sensitive and accurate for detecting mycobacteria and for differentiating MTB from NTM in clinical sputum smears.

• Tuberculosis and Respiratory Diseases
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• v.41 no.4
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• pp.339-353
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• 1994

Background : The p53 gene codes for a DNA-binding nuclear phosphoprotein that appears to inhibit the progression of cells from the G1 to the S phase of the cell cycle. Mutations of the p53 gene are common in a wide variety of human cancers, including lung cancer. In lung cancers, point mutations of the p53 gene have been found in all histological types including approximately 45% of resected NSCLC and even more frequently in SCLC specimens. Mutant forms of the p53 protein have transforming activity and interfere with the cell-cycle regulatory function of the wild-type protein. The majority of p53 gene mutations produce proteins with altered conformation and prolonged half life; these mutant proteins accumulate in the cell nucleus and can be detected by immunohistochemical staining. But protein overexpression has been reported in the absence of mutation. p53 protein overexpression or gene mutation is reported poor prognostic factor in breast cancer, but in lung cancer, its prognostic significance is controversial. Method : We investigated the p53 abnormalities by nucleotide sequencing, polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP), and immunohistochemical staining. We correlated these results with each other and survival in 75 patients with NSCLC resected with curative intent. Overexpression of the p53 protein was studied immunohistochemically in archival paraffin- embedded tumor samples using the D07(Novocastra, U.K.) antibody. Overexpression of p53 protein was defined by the nuclear staining of greater than 25% immunopositive cells in tumors. Detection of p53 gene mutation was done by PCR-SSCP and nucleotide sequencing from the exon 5-9 of p53 gene. Result: 1) Of the 75 patients, 36%(27/75) showed p53 overexpression by immunohistochemical stain. There was no survival difference between positive and negative p53 immunostaining(overall median survival of 26 months, disease free median survival of 13 months in both groups). 2) By PCR-SSCP, 27.6%(16/58) of the patients showed mobility shift. There was no significant difference in survival according to mobility shift(overall median survival of 27 in patients without mobility shift vs 20 months in patients with mobility shift, disease free median survival of 8 months vs 10 months respectively). 3) Nucleotide sequence was analysed from 29 patients, and 34.5%(10/29) had mutant p53 sequence. Patients with the presence of gene mutations showed tendency to shortened survival compared with the patients with no mutation(overall median survival of 22 vs 27 months, disease free median survival of 10 vs 20 months), but there was no statistical significance. 4) The sensitivity and specificity of immunostain based on PCR-SSCP was 67.0%, 74.0%, and that of the PCR-SSCP based on the nucleotide sequencing was 91.8%, 96.2% respectively. The concordance rate between the immunostain and PCR-SSCP was 62.5%, and the rate between the PCR-SSCP and nucleotide sequencing was 95.3%. Conclusion : In terms of detection of p53 gene mutation, PCR-SSCP was superior to immunostaining. p53 gene abnormalities either overexpression or mutation were not a significant prognostic factor in NSCLC patients resected with curative intent. However, patients with the mutated p53 gene showed the trends of early relapse.

• Tuberculosis and Respiratory Diseases
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• v.59 no.3
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• pp.286-297
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• 2005

Background : Non-small cell lung cancer (NSCLC) is a common cause of cancer-related death in North America and Korea, with an overall 5-year survival rate of between 4 and 14%. The TNM staging system is the best prognostic index for operable NSCLC . However, epidermal growth factor receptor (EGFR), matrix metalloproteinase-9(MMP-9), and C-erbB-2 have all been implicated in the pathogenesis of NSCLC and might provide prognostic information. Methods : Immunohistochemical staining of 81 specimens from a resected primary non-small cell lung cancer was evaluated in order to determine the role of the biological markers on NSCLC . Immunohistochemical staining for EGFR, MMP-9, and C-erbB-2 was performed on paraffin-embedded tissue sections to observe the expression pattern according to the pathologic type and surgical staging. The correlations between the expression of each biological marker and the survival time was determined. Results : When positive immunohistochemical staining was defined as the extent area>20%(more than Grade 2), the positive rates for EGFR, MMP-9, and C-erbB-2 staining were 71.6%, 44.3%, and 24.1% of the 81 patients, respectively. The positive rates of EGFR and MMP-9 stain for NSCLC according to the surgical stages I, II, and IIIa were 75.0% and 41.7%, 66.7% and 47.6%, and 76.9% and 46.2%, respectively. The median survival time of the EGFR(-) group, 71.8 months, was significantly longer than that of the EGFR(+) group, 33.5 months.(p=0.018, Kaplan-Meier Method, log-rank test).. The MMP-9(+) group had a shorter median survival time than the MMP-9(-) group, 35.0 and 65.3 months, respectively (p=0.2). The co-expression of EGFR and MMP-9 was associated with a worse prognosis with a median survival time of 26.9 months, when compared with the 77 months for both negative-expression groups (p=0.0023). There were no significant differences between the C-erbB-2(+) and C-erbB-2 (-) groups. Conclusion : In NSCLC, the expression of EGFR might be a prognostic factor, and the co-expression of EGFR and MMP-9 was found to be associated with a poor prognosis. However, C-erbB-2 expression had no prognostic significance.

• Radiation Oncology Journal
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• v.15 no.2
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• pp.79-95
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• 1997

Purpose : Phospholipase C(PLC) isozymes play significant roles in signal transduction mechanism. $PLC-\gamma$ 1 is one of the key regulatory enzymes in signal transduction for cellular proliferation and differentiation. Ras oncoprotein, EGFR, and PKC are also known to be involved in cell growth. The exact mechanisms of these signal transduction following irradiation, however, were not clearly documented Thus, this study was Planned to determine the biological significance of PLC, ras oncoprotein, EGFR, and PKC in damage and regeneration of rat intestinal mucosa following irradiation. Material and Method : Sixty Sprague-Dawley rats were irradiated to entire body with a single dose of 8Gy. The rats were divided into S groups according to the sacrifice days after irradiation. The expression of PLC, ras oncoprotein, EGFR and PKC in each group were examined by the immunoblotting and immunohistochemistry. The histopathologic findings were observed using H&I stain, and the mitoses for the evidence of regeneration were counted using the light microscopy & PCNA kit. The Phosphoinositide(PI) hydrolyzing activity assay was also done for the indirect evaluation of $PLC-\gamma$ 1 activity. Results: In the immunohistochemistry , the expression of $PLC-{\beta}$ was negative for all grøups. The expression of $PLC-{\gamma}1$ was highest in the group III followed by group II in the proliferative zone of mucosa. The expression of $PKC-{\delta}1$ was strongly positive in group 1 followed by group II in the damaged surface epithelium. The above findings were also confirttled in the immunoblotting study. In the immunoblotting study, the expressions of $PLC-{\beta}$, $PLC-{\gamma}1$, and $PKC-{\delta}1$ were the same as the results of immunohis-tochemistry. The expression of ras oncoprctein was weakly positive in groups II, III and IV. The of EGFR was the highest in the group II, III, follwed by group IV and the expression of PKC was weakly positive in the group II and III. Conclusion: $PLC-{\gamma}1$ mediated signal transduction including ras oncoprotein, EGFR, and PKC play a significant role in mucosal regeneration after irradiation. $PLC-{\delta}1$ mediated signal transduction might have an important role in mucosal damage after irradiation. Further studies will be necessary to confirm the signal transduction mediating the $PKC-{\delta}1$.

• Tuberculosis and Respiratory Diseases
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• v.45 no.2
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• pp.290-300
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• 1998

Background: CYFRA 21-1 is a tumor marker which measures a fragment of cytokeratin 19 expressed by epithelial cells in bronchus. It is known that cytokeratin 19 is abundant in squamous epithelial cell cancer of the lung. However, if the incidence of elevated serum CYFRA 21-1 level in patients with benign lung diseases or pulmonary tuberculosis with severe parenchymal damage is high the specificity of CYFRA 21-1 could be decreased. The purpose of this study is to investigate the changes of serum CYFRA 21-1 according to the degree of parenchymal damage and the usefulness of CYFRA 21-1 for diagnosing possibly combined lung cancer in patients with pulmonary tuberculosis. Method: We studied the changes of serum CYFRA 21-1 according to the sputum AFB stain, radiologic manifestation and history of treatment in 81 patients with pulmonary tuberculosis, and 20 healthy persons, 25 patients with lung cancer, as a control group. CYFRA 21-1 concentration in serum was quantified by the immunoradiometry assay(Centocor$^{(R)}$). Result: The results were as follow; Serum CYFRA 21-1 level was significantly lower in patients with pulmonary tuberculosis($1.54{\pm}1.19ng/mL$, p<0.01) as compared to patients with lung cancer($12.25{\pm}15.97ng/mL$), and was slightly higher than the level in heathy persons($0.90{\pm}0.49ng/mL$) but there was no significant difference. Serum CYFRA 21-1 level was below the cut-off value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis but it was above the cut-off value in 64 percent of patients with lung cancer. Serum CYFRA 21-1 level was significantly higher in the initial treatment group($1.91{\pm}1.55ng/mL$, p<0.05) as compared to the treatment. failure group ($0.92{\pm}0.30ng/mL$). According to the sputum AFB smear, serum CYFRA 21-1 level in patients with negative result was slightly higher than the level in patients with positive result but there was no significant difference. According to the radiologic manifestation, serum CYFRA 21-1 level was significantly higher in patients with infiltrative lesion ($2.15{\pm}1.63ng/mL$, p<0.01) as compared to patients with destructive lesion ($l.04{\pm}0.54ng/mL$). As the size of cavity or destructive lesion was larger, the level was significantly lower(p<0.05). Conclusion: As serum CYFRA 21-1 level was significantly higher in the initial treatment group and patients with infiltrative lesion, it suppose to be closely related with the degree of parenchymal damage of the lung of the pulmonary tuberculosis. However CYFRA 21-1 could be useful method for diagnosing lung cancer even in patients with pulmonary tuberculosis combined with lung cancer because of the fact that it was below the cutoff value of 3.3ng/mL in 95 percent of patients with pulmonary tuberculosis.