• Journal of Yeungnam Medical Science
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• v.15 no.2
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• pp.195-207
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• 1998

폐암을 집단 검진으로 조기 진단하려는 노력은 현재까지 뚜렷한 성과를 얻지 못하고 있는 실정이다. 미국의 국립암연구소에서 실시한 흉부엑스선 촬영과 객담세포진 검사를 이용한 폐암의 집단 검진 결과는 검진군에서 대조군보다 유의하게 진단율이 높았으며 절제율도 더 높았고 5년 생존율도 향상시킬 수 있었다. 그러나 폐암을 조기 진단하기 위한 집단 검진의 궁극적인 목표인 사망률을 감소시키지는 못하였다. 최근에는 미국 국립암 연구기관에서 실시했던 결과에 대한 해석이 다양하여 아직까지도 폐암 조기 진단에 있어서 흉부액스선촬영과 객담세포진검사의 의의에 관한 결론에 대해서는 논란이 되고 있다. 1993년부터 새로운 집단 검진에 관한 연구가 진행중에 있어서 그 결과가 나올 때까지는 흉부엑스선촬영과 객담세포진검사를 이용한 집단 검진의 의의에 대한 결과는 기다려 보아야 할 것이다. 분자생물학적으로 폐암을 조기 검진하기 위한 검체로는 혈액보다는 객담이 훨씬 적절하고 합리적인 검체이다. 폐암의 발생은 가장 먼저 기관지 상피 세포에서 일어나서 암화 과정의 여러 단계에서 다양한 종양 표지자가 객담에 섞여 나오기 때문에 이 표지자를 객담에서 측정하는 것이 훨씬 합리적인 조기 진단법이 될 수 있다. 동시에 폐암을 집단 검진으로 조기 진단하기 위해서는 종양 표지자를 대량으로 측정하기 위한 자동측정법도 개발되어야 할 것이다. 암을 예방하기 위하여는 여러면에서 방안이 연구되어야 한다. 즉 암발생의 가능성이 높은 대상을 선태하여야 하며 초기에 집단 검진으로 진단을 할 수 있어야 하고, 이러한 검진으로 추적 검사가 가능하여야 하며 마지막으로 결과를 판정할 수 있어야 한다. 이 가운데 현재까지 유일하게 실시할 수 없는 것은 조기 진단으로 사용할 수 있는 뚜렷한 종양 표지자가 없는 것이다. 이와 같이 현재까지는 폐암을 조기 진단하기 위한 특이한 표지자는 없으나 앞으로 폐암 발생 기전의 여러 단계가 체계적으로 밝혀진다면 그 과정에서 중요한 표지자들이 밝혀질 것이다. 그리고 이들을 간단하게 검사할 수 있는 검사법도 밝혀져 폐암 조기 진단의 궁극적 목적인 폐암으로 인한 사망률을 감소시킬 수 있을 것으로 기대된다.

• Tuberculosis and Respiratory Diseases
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• v.41 no.3
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• pp.277-288
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• 1994

Objectives : Multiple lung cancers and/or precancerous lesions can be developed because many bronchi are exposed to carcinogens simultaneously according to the concept of "Field Cancerization". We had performed a careful bronchoscopic examination and analysed the patients of double bronchial lesions who received the separate pathologic evaluation. Methods : We studied 21 patients of double bronchial lesions among 1855 patients of bronchoscopic examination from April 1990 to December 1993 in Korea Cancer Center Hospital. We classified the patients into three groups(double malignancies of different histology, double malignancies of same histology, and combination of malignant and benign lesions) and analysed the histologic type, location, radiologic findings, and clinical parameters. Results : Among 21 patients, six patients had double malignancies of different histology, eight had double malignancies of same histology, and seven had combination of malignant and benign lesions. Out of 14 double malignant cases, 11 cases are considered as synchronous multiple primary lung cancers. Combination of squamous cell carcinomas was found in 5 cases, combination of small cell carcinoma and squamous cell carcinoma was found in 4 cases. Combination of adenocarcinoma and squamous cell carcinoma and combination of squamous cell carcinoma and poorly differentiated carcinoma were found in 1 case respectively. All patients of synchtonous multiple primary lung cancers were male and had long smoking history(average 40 pack years). Among 21 cases of double bronchial lesions, only one lesion could be detected by prebronchoscopic radiologic examination including chest CT in 15 cases. Conclusions : The presence of double bronchial lesions including multiple primary lung cancers and the limitation of radiologic examination to detect early bronchial lesions encourage us to examine the whole bronchi carefully and to perform pathologic evaluations.

• Journal of Yeungnam Medical Science
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• v.1 no.1
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• pp.139-144
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• 1984

A case of foregut cyst communicated with esophagus and lined by bronchial mucosa is reviewed and its embryologic base of maldevelopment is discussed. It is not always easy to distinguish between digestive and respiratory cyst in mediastinum. There is whole range of intermediate between a cyst with ciliated and one with squamous or columnar mucosa. Origin of this dysembryoplasia is difficult to determine when one consider that the esophagus is covered with ciliated epithelium until the eleventh week of fetal life and that ciliated growth are found on its wall until the sixth month of the fetal life. And we concluded, general agreement is that cysts which have gastric epithelium in whole or in part, represent a distinct type and should be classified as (gastro) enteric cyst, mediastinal cyst containing cartilage were considered definitely as respiratory(bronchial or bronchogenic) cyst.

• Tuberculosis and Respiratory Diseases
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• v.59 no.2
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• pp.142-150
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• 2005

Background : Continuous growth stimulation by various factors, as well as chronic oxidative stress, may co-exist in many solid tumors, such as lung cancer. A new family of antioxidant proteins, the peroxiredoxins (Prxs), have been implicated in the regulation of many cellular processes, including cell proliferation, differentiation and apoptosis. However, a real pathophysiological significance of Prx proteins, especially in lung disease, has not been sufficiently defined. Therefore, this study was conducted to investigate the distribution and expression of various Prx isoforms in lung cancer and other pulmonary conditions. Method : Patients diagnosed with lung cancer, and who underwent surgery at the Ajou Medical Center, were enrolled. The expressions of Prxs, Thioredoxin (Trx) and Thioredoxin reductase (TR) were analyzed using proteomic techniques and the subcellular localization of Prx proteins was studied using immunohistochemistry on normal mouse lung tissue. Result : Immunohistochemical staining has shown the isoforms of Prx I, II, III and V are predominantly expressed in bronchial and alveolar lining epithelia, as well as in the alveolar macrophages of the normal mouse lung. The isoforms of Prx I and III, and thioredoxin were also found to be over-expressed in the lung cancer tissues compared to their paired normal lung controls. There was also an increased amount of the oxidized form of Prx I, as well as a putative truncated form of Prx III, in the lung cancer samples when analyzed using 2-dimensional electrophoresis. In addition, a 43 kDa intermediate molecular weight protein band, and other high molecular weight bands of over 20 kDa, recognized by the anti-Prx I antibody, were present in the tissue extracts of lung cancer patients on 1-Dimensional electrophoresis, which require further investigation. Conclusion : The over-expressions of Prx I and III, and Trx in human lung cancer tissue, as well as their possible chaperoning function, may represent an attempt by tumor cells to adjust to their microenvironment in a manner advantageous to their survival and proliferation, while maintaining their malignant potential.

• Tuberculosis and Respiratory Diseases
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• v.45 no.4
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• pp.760-765
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• 1998

Background: Glucose uptake has been found to be increased in cancer cells, and FDG-PET imaging is used for diagnosis of cancer using this phenomenon. However, the exact mechanism of increased glucose uptake in cancer cells has not been clarified. Recent studies demonstrated the presence of glucose transporter(GLUT) mRNA expression in gastrointestinal cancer and head and neck cancer, and suggested that GLUT may be associated with glucose uptake in cancer cells. In lung cancer cells, glucose metabolism is also known to be increased. We evaluated GLUT mRNA expression in human lung cancer cell lines in order to find out the mechanism of increased glucose uptake in lung cancer. Method: Total RNA was isolated from 15 human lung cancer cell lines and immortalized bronchial epithelial cell line(BEAS-2B). After electrophoresis of $20{\mu}g$ total RNA, Northern blot analysis was done using GLUT1 cDNA and GLUT3 cDNA as probes. Results: Thirteen of 14 human lung cancer cell lines expressed GLUT1 mRNA and 10 of 14 human lung cancer cell lines expressed GLUT3 mRNA. Eight human lung cancer cell lines expressed both GLUT mRNAs. BEAS-2B expressed GLUT1 mRNA and did not express detectable GLUT3 mRNA. Conclusion: The increase of glucose metabolism in lung cancer may be associated with GLUT1 and GLUT3 expression.

• The Journal of Korean Medicine
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• v.24 no.1
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• pp.74-83
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• 2003

Background : Production of cytokines by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the dose-dependent inhibitory effects of Socheongryong-tang and Socheongryong-tang plus Sasam (Adenophorae Radix) on the mRNA expressions of Interleukin (IL)-6, IL-8 and granulocyte macrophage colony stimulating factor (GM-CSF) involved in the asthma model. Materials and Methods : In this study, BEAS-2B cell lines, human epithelial cells, were used. These cells were stimulated by tumor necrosis factor $(TNF)-{\alpha},{\;}IL-1{\beta}$ and histamine for artificial inflammatory expression. ${\beta}-actin$ messenger RNA (mRNA) was used for the internal standard. After each 24 hours of the Socheongryong-tang (小靑龍湯) and Socheongryong-tang plus Sasam (小靑 龍湯加沙蔘) treatment, total cellular RNAs were collected by applying RNAzol directly to the living cells. Then the transcriptional activities of IL-6, IL-8 and GM-CSF were measured by RT-PCR with electrophoresis. Results : In the Socheongryong-tang (小靑龍湯) study, the mRNA expressions of IL-6, IL-8 and GM-CSF were significantly inhibited compared to that of the control group (p<0.05). In the Socheongryong-tang plus Sasam (小靑龍湯加沙蔘) study, the mRNA expressions of IL-6, IL-8 and GM-CSF were significantly inhibited compared to that of the control group (p<0.05). Conclusions : This study shows that Socheongryong-tang (小靑龍湯) and Socheongryong-tang plus Sasam (小靑龍湯加沙蔘) have dose-dependent inhibitory effects on the mRNA expressions of IL-6, IL-8 and GM-CSF in human epithelial cells, so these herbal medicines may inhibit the inflammatory process of asthma. Advanced studies are required to investigate the mechanisms of inhibition by herbal medicine in the asthma model.

• The Journal of Korean Medicine
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• v.24 no.3
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• pp.145-154
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• 2003

Background : Production of cytokines by bronchial epithelial cells may contribute to the local accumulation of inflammatory cells in patients with bronchial asthma. In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Objective : We aimed to identify the dose-dependent inhibitory effects of Lonicerae Flos and Paeoniae Radix on the mRNA expression of IL-6, IL-16, and GM-CSF involved in the asthma model. Materials and Methods : In the study BEAS-2B cell lines, human epithelial cells were used. These cells were stimulated with tumor necrosis factor $(TNF)-\alpha$ for artificial inflammatory expression. ${\beta}-actin$ messenger RNA (mRNA) was used for internal standard. After 24 hours of Lonicerae Flos, Paeoniae Radix, total cellular RNAs were collected treating RNA zol directly on the living cells. Then the transcriptional activities of IL-6, 16, GM-CSF were measured by RT- PCR with electrophoresis. Results : In the Lonicerae Flos study, the mRNA expression of IL-6, IL-16 and GM-CSF was showed no inhibitory effect compared to the control group in all concentrations. In the Paeoniae Radix study, the mRNA expression of IL-6, IL-l6 and GM-CSF was showed no inhibitory effect compared to the control group in all concentrations. Conclusion : This study shows that Lonicerae Flus and Paeuniae Radix have no inhibitory effects on the mRNA expression of IL-6, IL-16 and GM-CSF in BEAS-2B cell lines, human epithelial cells. Advanced studies are required to investigate the other mechanisms of inhibitory effect by Lonicerae Flus and Paeoniae Radix in the asthma model.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.210-220
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• 1996

Background : Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. In the process of surface adherence, adhesion molecules have a clear role in intracellular signal pathway of cellular activation. Human alveolar macrophages(HAM) are frequently purified by the adherence procedure after bronchoalveolar lavage. But the experimental data of many reports about alveolar macrophages have ignored the possibility of adhesion-induced cellular activation. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be normal by chest CT. With the measurement of hydrogen peroxide release from adherent HAM to plastic surface and non-adherent HAM with or without additional stimulation of phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), we observed the effect of the adherence to plastic surface. We also evaluated the effect of various biological surfaces on adhesion-induced activation of HAM. Then, to define the intracellular pathway of signal transduction, pretreatment with cycloheximide, pertussis toxin and anti-CD11/CD18 monoclonal antibody was done and we measured hydrogen peroxide in the culture supernatant of HAM. Results : 1) The adherence itself to plastic surface directly stimulated hydrogen peroxide release from human alveolar macrophages and chemical stimuli such as phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine(fMLP) colud not increase hydrogen peroxide release in these adherent macrophages which is already activated. 2) PMA activated human alveolar macrophages irrespective of the state of adhesion. However, fMLP stimulated the release of hydrogen peroxide from the adherent macrophages, but not from the non-adherent macrophages. 3) HAM adherent to A549 cell(type II alveolar epithelium-like human cell line) monolayer released more hydrogen peroxide in response to both PMA and fMLP. This adherence-dependent effect of fMLP was blocked by pretreatment of macrophages with cycloheximide, pertussis toxin and anti-CD18 monoclonal antibody, Conclusion : These results suggest that the stimulatory effect of PMA and fMLP can not be found in adherent macrophage because of the activation of human alveolar macrophage by the adherence to plastic surface and the cells adhered to biologic surface such as alveolar epithelial cells are appropriately responsive to these stimuli. It is also likely that the effect of fMLP on the adherent macrophage requires new protein synthesis via G protein pathway and is dependent on the adhesion between alveolar macrophages and alveolar epithelial cells by virtue of CD11/CD18 adhesion molecules.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.16 no.3
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• pp.82-95
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• 2003

Chemokines are important for the recruitment of leukocytes to sites of infection, which is essential in host defense. The thymus and activation-regulated chemokine (TARC) is a CC chemokine which potentially plays a role via a paracrine mechanism in the development of allergic respiratory diseases. Objectives : The objective of this study is to investigate the effect of Youn-Gyo-Pae-Doc-San on the secretion of TARC of human bronchial epithelial cell Methods : Enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion of TARC. The cytotoxicity was measured by MTT assay. Results : Youn-Gyo-Pae-Doc-San significantly inhibited the secretion of TARC with a dose -dependant manner. The effective dosage did not have the cytotoxicity on human bronchial epithelial cell. Conclusions : Results of our study show that Youn-Gyo-Pae-Doc-San would play an important role in modulation of TARC in human bronchial epithelial cells.

• Environmental Analysis Health and Toxicology
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• v.21 no.4 s.55
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• pp.357-363
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• 2006

Chromium compounds are widely used in diverse industries including pigment manufacturing, painting, metal plating and leather tanning. With the wide uses of chromium, various adverse effects of the compounds on the environment and human health have been reported. Among them, hexavalent chromium [Cr (VI)], which is a carcinogenic heavy metal, has been widely studies. Epidemiological investigations have shown that respiratory cancers had been found in workers who had been occupationally exposed to Cr (VI). In this study, cell toxicity and induction of reactive oxygen species (ROS) by Cr (VI) (1, 2, 4, $8{\mu}M$) in cultured human bronchial epithelial cells were investigated. Exposure of the cells to Cr (VI) led to cell death, ROS increase, and cytosolic caspase-3 activation. The ROS increase was related with the decreased level of GSH. Chromatin condensation and fragmentation were occurred by Cr (VI) when evaluated by DAPI staining or agarose gel electrophoresis of the extracted DNA. Expression of ROS related genes including glutathione S-transferase, heme oxygenase-1, metallothionein were significantly induced in Cr (VI) treated cells. This result suggests the toxicity in cultured cells by Cr (VI) was expressed through the apoptotic process with ROS induction.