• Archives of Pharmacal Research
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• 제29권8호
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• pp.651-656
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• 2006

This study examined the chemopreventive effect of saponins that were isolated from the roots of Platycodon grandiflorum A. DC (Campanulaceae), Changkil saponins (CKS), against the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), -on lung tumorigenesis in A/J mice. The mice were treated with a single NNK dose (100 mg/kg b.w., i.p.). CKS (0.5, 1, 4 mg/kg body wt.) was administered orally daily for 3 days/week beginning 1 day after the NNK treatment and was maintained throughout the experiment. The administration of CKS suppressed the NNK-induced increase in the level of proliferating cell nuclear antigen, which are a marker of cell proliferation, in the lungs of the mice 4 weeks after the NNK injection. Twenty-five weeks after the NNK treatment, the mice were sacrificed and the number of surface lung tumors was measured. CKS significantly reduced the number of lung tumors induced by NNK in a dose dependent manner. These results suggest that CKS suppresses the development of lung tumors and has a chemopreventive effect against NNK-induced mouse lung tumorigenesis.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5233-5237
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• 2014

Epigenetic modifications of tumour suppressor genes are involved in all kinds of human cancer. Aberrant promoter methylation is also considered to play an essential role in development of lung cancer, but the pathogenesis remains unclear.We collected the data of 112 subjects, including 56 diagnosed patients with lung cancer and 56 controls without cancer. Methylation of the FHIT, RASSF1A and RAR-${\beta}$ genes in DNA from all samples and the corresponding gene methylation status were assessed using the methylation-specific polymerase chain reaction (PCR, MSP). The results showed that the total frequency of separate gene methylation was significantly higher in lung cancer compared with controls (33.9-85.7 vs 0 %) (p<0.01).Similar outcomes were obtained from the aberrant methylation of combinations of any two or three genes (p<0.01). There was a tendency that the frequency of combinations of any two or three genes was higher in stage I+II than that in stage III+IV with lung cancer. However, no significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis. Methylation of FHIT, RASSF1A and $RAR{\beta}$ genes may be related to progression of lung oncogenesis.

• Journal of Chest Surgery
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• 제50권6호
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• pp.424-429
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• 2017

Background: The surgical treatment of secondary spontaneous pneumothorax (SSP) can be complicated by fragile lung parenchyma. The preoperative prediction of air leakage could help prevent intraoperative lung injury during manipulation of the lung. Common sites of bulla development and ruptured bullae were investigated based on computed tomography (CT) and intraoperative findings. Methods: The study enrolled 208 patients with SSP who underwent air leak control through video-assisted thoracoscopic surgery (VATS). We retrospectively reviewed the sites of bulla development on preoperative CT and the rupture sites during VATS. Results: Of the 135 cases of right-sided SSP, the most common rupture site was the apical segment (31.9%), followed by the azygoesophageal recess (27.4%). Of the 75 cases on the left side, the most common rupture site was the apical segment (24.0%), followed by the anterior basal segment (17.3%). Conclusion: The azygoesophageal recess and parenchyma along the cardiac border were common sites of bulla development and rupture. Studies of respiratory lung motion to measure the pleural pressure at the lung surface could help to determine the relationship between cardiogenic and diaphragmatic movement and bulla formation or rupture.

• 한국동물위생학회지
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• 제20권1호
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• pp.55-67
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• 1997

The morphological development of lungs in fetuses of 60, 90 and 120 days of gestation and neonates of Korean native goats was investigated by light, scanning and transmission electron mictroscope. The results were summarized as follows ; 1. Gross findings ; In the 60-days-old fetus, the lung was developed and differentiated into six lobes. 2. Light microscopic findings : The gland-like bronchioles were formed in loose mesenchyme at 60 days of gestation and the bronchial wall contained smooth muscles. The loose mesenchyme had been replaced by compact parenchymal tissue at 90 days of gestation and the cartilage plates appeared in bronchial wall which contained blood vessels, submucosal glands and smooth muscles. The lung parenchyma consisted of a fine network of alveoli at 120 days of gestation and the bronchial wall contained well-developed blood vessels, submucosal glands, cartilage plates and smooth muscles. In neonates, the lung tissue was similar to the mature lung tissue and the bronchial wall contained well developed cartilage plates. 3. Scanning electron microscopic findings : The epithelial cells lining the tubules were composed of cuboidal or columnar at 60 days of gestation and the epithelial cells lining the large airways were often ciliated : some were covered with stubby microvilli. The epithelial cells lining the canals were cuboidal at 90 days of gestation and the epithelial cells lining the bronchioles were ciliated cells or nonciliated(clara) cells, The clara cells contained row microvilli. The alvealor development of this stage was rapidly progressed ; the subdivision of canals by alveolar crests and assosiated wall attenuation resulted alveoli at 120 days of gestation and the respiratory bronchioles were lined by ciliated or nonciliated epithelial cells. In neonates, the epithelial cells lining the alveolar walls were mainly covered with pneumocyte type I ; Some were covered with pneu-mocyte type II. 4. Transmission electron microscopic findings : The epithelial cells lining the tubules were adhered with tight junction at apical borders of the adjacent cells at 60 days of gestation, which contained few organells and glycogen. The epithelial cells lining the canals were composed mostly of cuboidal cell at 90 days of gestation and the epithelial cells lining of the bronchioles were ciliated of nonciliated cell, which contained few organelles and abundant glycogen. The epithelial cells lining the alveolar walls were composed of pneumocyte type I and a few pneumocyte type II at 120 days of gestation. The epithelial cells lining of the bronchioles were ciliated or nonciliated cells. In neonates, pneumocyte type I was observed as flat and thin cytoplasmic extension in shape. Otherwise, pneumocyte type II was observed as cuboidal type with apical microvilli and contained osmiophillic lamellar inclusion bodies. Putting these various experiment results together, the lung development was slowly progressed at early stage, which was rapidly progressed in the late stage of gestation.

• Asian Pacific Journal of Cancer Prevention
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• 제15권9호
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• pp.4095-4099
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• 2014

The X-ray repair cross-complementing group 1 protein (XRCC1) plays important roles in the DNA base excision repair pathway which may influence the development of lung cancer. This study aimed to evaluate the potential association of the XRCC1 c.1178G>A genetic polymorphism with lung cancer risk. The created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were utilized to evaluate the XRCC1 c.1178G>A genetic polymorphism among 376 lung cancer patients and 379 controls. Associations between the genetic polymorphism and lung cancer risk were determined with an unconditional logistic regression model. Our data suggested that the distribution of allele and genotype in lung cancer patients was significantly different from that of controls. The XRCC1 c.1178G>A genetic polymorphism was associated with an increased risk of lung cancer (AA vs GG: OR=2.91, 95%CI 1.70-4.98, p<0.001; A vs G: OR=1.52, 95%CI 1.22-1.90, p<0.001). The allele A and genotype AA may contribute to risk of lung cancer. These preliminary results suggested that the XRCC1 c.1178G>A genetic polymorphism is statistically associated with lung cancer risk in the Chinese population.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3817-3822
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• 2016

Background: Lung cancer has long been a leading cause of cancer related death in both women and men worldwide. The focus of this study was to review clinicopathological features of Iranian patients diagnosed with lung cancer. Materials and Methods: Clinicopathological data of 1353 primary lung cancer patients diagnosed during 17 years (1997-2014) in the "National Institute of Tuberculosis and Lung Disease" (NRITLD), Tehran, Iran, were retrospectively reviewed. Results: The median age of patients was 60 (mean: 58.95 years, range: 16-99) and adenocarcinoma was the most prevalent pathology (45.2%). Male/female ratio was 3.22 and 57.2% of patients were smokers (men 70.3%, women 15%). The majority (85.3%) were referred in advanced stages (stage IIIB and IV). Conclusions: Although some of our findings are in concordance with other studies in lung cancer but there are some discrepancies particularly in terms of smoking status and median age of Iranian patients. Further clinical and epidemiological studies are warranted to elucidate etiologic and factors other than smoking contributing to development of lung cancer such as environmental exposures or genetic predisposition.

• Tuberculosis and Respiratory Diseases
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• 제74권3호
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• pp.129-133
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• 2013

The presence of epidermal growth factor receptor (EGFR ) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1547-1551
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• 2012

Background: Lung cancer is the leading cause of cancer morbidity and mortality. Its management has a significant economic impact on society. Despite a high incidence of cancer, so far, there is no national register for this disease in Morocco. The main goal of this report was to estimate the medical costs of lung cancer in our country. Methods: We first estimated the number of annual new cases according to stage of the disease on the basis of the Grand-Casablanca-Region Cancer Registry data. For each sub-group, the protocol of treatment was described taking into account the international guidelines, and an evaluation of individual costs during the first year following diagnosis was made. Extrapolation of the results to the whole country was used to calculate the total annual cost of treatments for lung cancer in Morocco. Results: Overall approximately 3,500 new cases of lung cancer occur each year in the country. Stages I and II account for only 4% of cases, while 96% are diagnosed at locally advanced or metastatic stages III and IV. The total medical cost of lung cancer in Morocco is estimated to be around USD 12 million. This cost represents approximately 1% of the global budget of the Health Department. According to AROME Guidelines, about 86% of the newly diagnosed lung cancer cases needed palliative treatment while 14% required curative intent therapy. The total cost of early and advanced stages lung cancer management during the first year were estimated to be 4,600 and 3,420 USD, respectively. Conclusion: This study provides health decision-makers with a first estimate of costs and the opportunity to achieve the optimal use of available data to estimate the needs of health facilities in Morocco. A substantial proportion of the burden of lung cancer could be prevented through the application of existing cancer control knowledge and by implementing tobacco control programs.

• 한국동물위생학회지
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• 제41권4호
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• pp.263-269
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• 2018

Developing drugs targeting respiratory pathogen is essential to control respiratory diseases. Many experiments have been performed under in vivo situation. However, in vivo experiments have economical and ethical issues. The objective of this study was to determine the possibility of developing an ex vivo lung culture system with possible application for respiratory infection studies. After isolating lungs from naïve pigs, agarose-inflated lung tissues were prepared and sliced manually. These sliced lung tissues were then subsequently placed on 24-well plates. Eight different combinations of media were used to determine the optimum ex vivo lung culture condition. In addition, lung tissues were infected with porcine reproductive and respiratory syndrome (PRRS) virus at a titer of $1{\times}10^4\;TCID_{50}/mL$. Virus growth was confirmed by titration in MARC-145 cells at 2, 4, 6 days post infection (dpi). We found that ex vivo lung culture in physiological environment was not media specific based on histopathology and cytotoxicity. However, under virus-infected condition, thickened alveolar walls in the lung tissues and stable virus titers at 2, 4, 6 dpi were shown in F12K medium suggesting that it was useful for tissue maintenance and virus infection using PRRS virus infected lung tissues. The present study shows the possibility of using porcine ex vivo lung model for respiratory infection studies.

• 한국지능정보시스템학회:학술대회논문집
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• 한국지능정보시스템학회 2001년도 The Pacific Aisan Confrence On Intelligent Systems 2001
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• pp.378-382
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• 2001

The purpose of this study was to develop an expert system supporting the diagnosis of diffuse interstitial lung disease by high resolution computed tomography. CLIPS(C language integrated production system) with rule-based reasoning was used to develop the system. Development of expert system had three stages knowledge acquisition, knowledge representation, and reasoning. Knowledge was obtained and integrated, from tables and figure legends of a representative textbook in the domain of this expert system, High-Resolution CT of the Lung, by Webb WR, Mueller NL, and Naidich DP. The acquired knowledge was analyzed to form a knowledge base. Overlapping knowledge was eliminated, similar pieces of knowledge were combined and professional terms were defined. The most important knowledge of findings was then selected for each disease. After groupings of combined findings were made, disease groups were analyzed sequentially to determine final diagnoses. The system was based upon the input of 69 diseases, 185 findings, 73 conditions, 387 status, and 62 rules. The system was set up to determine the diagnoses of diseases from the combination of findings using forward reasoning. In an empirical trial, the system was applied to support the diagnosis of 40 cases of diffuse interstitial lung diseases. The performance of two doctors with support of the system was compared to that of another two doctors without support of the system. The two doctors with the support of the system made more accurate diagnoses than the doctors without the support of the system. The system is believed to be useful for the diagnosis of rare diseases and for cases with many possible differential diagnoses. In conclusion, an expert system supporting the high resolution computed tomographic diagnosis of diffuse interstitial lung disease was developed and the system is thought to be useful for medical practice.