• Journal of Microbiology and Biotechnology
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• 제28권3호
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• pp.425-431
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• 2018

Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, is a principal component of cigarette smoke. B[a]P can cause lung carcinogenesis and plays a key role in lung cancer progression. The role of B[a]P has been reported in lung cancer, but its effects on lung cancer stem cells (CSCs) have not been investigated. Emerging evidence indicates that CSCs are associated with carcinogenesis, tumor initiation, relapse, and metastasis. Therefore, targeting CSCs to defeat cancer is a challenging issue in the clinic. This study explored whether B[a]P alters gene expression in lung cancer cells and CSCs. The lung adenocarcinoma A549 cell line was used to investigate the role of B[a]P on lung cancer cells and lung CSCs using microarray and quantitative PCR. B[a]P ($1{\mu}M$) provoked gene expression changes in A549 cancer cells and CSCs by deregulating numerous genes. Gene pathway analysis was performed using GeneMANIA and GIANT. We identified genes that were coexpressed and showed physical interactions. These findings improve our understanding of the mechanism of B[a]P in lung cancer and cancer stem cells and can be an attractive therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• 제16권1호
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• pp.201-204
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• 2015

Background: This study was designed to determine the accuracy of bronchoalveolar lavage fluid cytology (BAL) using histopathologic examination of transbronchial biopsy specimens as the gold standard in diagnosis of lung carcinoma at our center. Materials and Methods: A retrospective study was conducted to investigate a total of 388 patients who were suspected of having lung cancer and had undergone fiberoptic bronchoscopy in Shahid Sadoughi hospital from 2006 to 2011. Lung masses were proven to be malignant by histology. Results: Transbronchial lung biopsy (TBLB) identified malignancy in 183 of the 388 cases, including 48 cases (26.2%) with adenocarcinoma, 4(2.1%) with bronchioloalveolar carcinoma, 47(25.6%)with squamous cell carcinoma, 34(18.5%) with well-diffentiated neuroendocrine carcinoma, 35(19.1%) with small cell carcinoma, 14 (7.6%) with non-small cell carcinoma, and 1 (0.54%) with large cell carcinoma. A total of 205 cases were correctly classified as negative. BAL was also performed in 388 patients; 86/103 cases were consistent with the final diagnosis of lung cancer and 188/285 cases were correctly classified as negative. The sensitivity of BAL was 46.9%(CI:41.9%, 51.8%)) and its specificity was 91.6%(CI:88.8%, 94.3%). BAL had a positive predictive value (PPV) of 83.4%(CI:79.7%, 87.1%) and a negative predictive value (NPV) of 65.8%(CI:61%, 70.5%). The overall accuracy of BAL was 70.5% and the exact concordance was 39%. Conclusions: Our findings suggest that BAL cytology is not sensitive but is a specific test for diagnosis of lung carcinoma. If transbronchial lung biopsy is combined with bronchoalveolar lavage, the positive diagnostic rate will be further elevated.

• 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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• 제24권4호
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• pp.376-381
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• 1991

From June 1979 to July 1988 for 9 years, total 440 cases of lung cancer[including biopsy and surgical specimen] of the Pusan Paik hospital were examined for the clinical and pathology study. The findings of the study are as follows; [1] The incidence of lung cancer started to increase from 1982, and it again remarkably increased since 1987. Such increase was solely brought by the increase of male lung cancer. Male and female ratio is 5.6: 1. [2] Histopathologically, the most prevalent type is squamous cell carcinoma[60.ado], and next are adenocarcinoma[15.6%] and small cell carcinoma[15.0%]. But in female alone, the most prevalent type is adenocarcinoma[40.3%], and next are squamous cell carcinoma[37.3%] and small cell carcinoma[11.9%]. [3] The absolute number of adenocarcinoma are approximately equally distributed among both sexes until 60 years of age. Above 61 years of age, mostly male was shown while female was not. Most probably, many female patient.- of that old age simply did not visit general hospitals for surgery in Korea. [4] Surgical treatment was performed in 8% of total cases of lung cancer. And most cases showed stage I progression of the cancer. Average size of the cancer was 5 cm in diameter in the operated 35 cases suggesting that the cancer could be detected more than 10 years ago before the time of surgery. [5] Lung cancer affected more in the right lung [right: left=1.6: 1], and each upper lobe of both lungs are affected about 1/4 of cases indicating that about 1/2 of all lung cancer develop from the upper lobes. [6] There are more nonsmokers[67.6%] among the lung cancer patients[male 64.6%, female 82.1%]. Probably, this will mean that there are other potent carcinogenic agents in our environment like automobile exhaust beside tobacco smoke. For the past history of lung disease other than cancer, tuberculosis is the most prevalent disease[16.1%, male 17.4%, female 9.0%]. Most of them is probably not related etiologically though this possibility is not completely denied.

• Applied Microscopy
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• 제15권1호
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• pp.101-111
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• 1985

A study was undertaken to observe the distribution and ultrastructure of the sensory papillae of the liver and lung flukes which was obtained from experimentally infected rats and dogs. For this study, the rats were artificially infected with metacercariae isolated from Pseudorasbora parve, and the dogs were artificially infected with metacercariae isolated from Cambaroides similis. The liver flukes (Clonorchis sinensis) were collected from the bile ducts of the rats which were autopsied 5 weeks later since infection. The lung flukes (Paragonimus westermani) were collected from the lung of the dogs which were autopsied 3 months later since infection. With the collected worms, ultrastructure of sensory papillae was studied by means of a scanning and transmission electron microscope. The liver flukes were compared with the lung flukes. The results of the observation are as follows. 1. The sensory papillae of the liver flukes was classified into 3 types and most of sensory papillae were distributed on the oral sucker. 2. The sensory papillae of the lung flukes were distinguished 8 types. The sensory papilla type VIII was specifically distributed on the oral sucker and type I, II were distributed on the tegumental surface of the worm. The sensory papillae of the lung flukes were mostly observed between oral sucker and ventral sucker of the worm excusively 3. The sensory papillae of the liver flukes were distributed around the sucker while those of the lung flukes were developed between spine. 4. The sensory papillae were formed by many tegumental ridge in the liver flukes while was made of many small sensory papillae in the lung flukes. 5. The sensory cilia were observed between tegumental ridges in the sensory papilla of the liver flukes and also in lung flukes. And they are alike in that respect. 6. The sensory papillae were not developed in the posterior part of the liver and lung flukes but mostly nerve endings were formed in the tegumental syncytium, and it was connected with neuropile.

• The Korean Journal of Physiology and Pharmacology
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• 제2권4호
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• pp.479-491
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• 1998

In order to know the pathogenesis of adult respiratory distress syndrome (ARDS) in association with the oxidative stress by neutrophils, the role of platelet activating factor (1-0-alkyl-2-acetyl-snglycero-3-phosphocholine, PAF) was investigated during acute lung injury induced by interleukin- $1{\alpha}$ (IL-1) in rats. An insufflation of IL-1 into the rat's trachea increased the acetyltransferase activity in the lung and the increase of PAF content was followed. As evidences of acute lung injury by neutrophilic respiratory burst, lung leak index, myeloperoxidase activity, numbers of neutrophils in the bronchoalveolar lavage fluid, neutrophilic adhesions to endothelial cells and NBT positive neutrophils were increased after IL-1 treatment. In addition, a direct instillation of PAF into the trachea caused acute lung leak and the experimental results showed a similar pattern in comparison with IL-1 induced acute lung injury. For the confirmation of oxidative stress during acute lung leak by IL-1 and PAF, a histochemical electron microscopy was performed. In IL-1 and PAF treated lungs of rats, the deposits of cerrous perhydroxide were found. To elucidate the role of PAF, an intravenous injection of PAF receptor antagonist, WEB 2086 was given immediately after IL-1 or PAF treatment. WEB 2086 decreased the production of hydrogen peroxide and the acute lung leak. In ultrastructural study, WEB 2086 mitigated the pathological changes induced by IL-1 or PAF. The nuclear factor kappa B (NFkB) was activated by PAF and this activation was inhibited by WEB 2086 almost completely. Based on these experimental results, it is suggested that the PAF produced in response to IL-1 through the remodeling pathway has the major role for acute lung injury by neutrophilic respiratory burst. In an additional experiment, we can also come to conclude that the activation of the NFkB by PAF is thought to be the fundamental mechanism to initiate the oxidative stress by neutrophils causing release of proinflammatory cytokines and activation of phospholipase $A_2$.

• Tuberculosis and Respiratory Diseases
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• 제71권3호
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• pp.216-220
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• 2011

Respiratory bronchiolitis-associated interstitial lung disease is one of the smoking-related interstitial lung diseases. Histopathologically, it shows respiratory bronchiolitis, which is characterized by the accumulation of pigmented macrophages within the respiratory bronchioles, accompanying peribronchiolar inflammation. Clinically, it is presented with respiratory symptoms such as a cough, sputum and dyspnea on exertion. It is well known that the incidence of malignancy in interstitial lung disease is high, but in respiratory bronchiolitis-associated interstitial lung disease the report of accompanying malignancy is rare. Here we report a case of a 60-year-old male heavy smoker presented with a cough, sputum and clubbing finger. A chest computed tomography (CT) of the patient did not show any shadow suspected of malignancy, but adenocarcinoma was found on a transbronchial lung biopsy and on a surgical lung biopsy with respiratory bronchiolitis-associated interstitial lung disease.

• 대한기관식도과학회지
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• 제6권2호
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• pp.159-163
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• 2000

The patient with findings of diffuse infiltrative lung on chest X-ray has various causes; therefore, the prognosis is different and the treatment should be changed according to the cause. We are trying to identify the meaning of operative lung biopsy and to 11nd a more accurate and effective procedure. We reviewed 46 medical records of patients with the findings of diffuse infiltrative lung on chest X-ray who had undergone operative lung biopsy or biopsies for 8 years. The open lung biopsy were done in 22 cases(47.8%) and thoracoscopic lung biopsy in 24 cases(52.2%). There is no significant difference in the rate of diagnosis(p=0.452) and the incidence of complications(p=0.155) between these groups. The number of cases with more than two biopsies are 9(19.6%) and that of one biopsy are 37(80.4%). There are no statistical difference in the rate of diagnosis(p=0.928) and the incidence of complications(p=0.125). The postoperative complications occurred in 8 cases,7 cases of air leak more than 7 days and 1 case of respiratory insufficiency. In the diagnosis and treatment of the patients with findings of infiltrative lung on chest X-ray, the operative lung biopsy is the very necessary course, and shows satisfactory rate of diagnosis with negligible complications.

• Tuberculosis and Respiratory Diseases
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• 제78권2호
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• pp.72-77
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• 2015

Background: Lung cancer is the most lethal type of cancer in the world. Several benign lung diseases may mimic lung carcinoma in its clinical and radiological presentation, which makes the differential diagnosis for granulomatous diseases more relevant in endemic regions like Brazil. This study was designed to describe the prevalence and the diagnostic work-up of benign diseases that mimic primary lung cancer in patients hospitalized at a university hospital from south of Brazil. Methods: This was a transversal study, which evaluated the medical records of 1,056 patients hospitalized for lung cancer treatment from September 2003 to September 2013 at University Hospital of Santa Maria. Results: Eight hundred and four patients underwent invasive procedures for suspected primary lung carcinoma. Primary lung cancer was confirmed in 77.4% of the patients. Benign disease was confirmed in 8% of all patients. Tuberculosis (n=14) and paracoccidioidomycosis (n=9) were the most frequent infectious diseases. The diagnosis of benign diseases was obtained by flexible bronchoscopy in 55.6% of the cases and by thoracotomy in 33.4%. Conclusion: Infectious diseases are the most frequent benign diseases mimicking lung cancer at their initial presentation. Many of these cases could be diagnosed by minimally invasive procedures such as flexible bronchoscopy. Benign diseases should be included in the differential diagnosis during the investigation for primary lung cancer in order to avoid higher cost procedures and mortality.

• Journal of Chest Surgery
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• 제30권6호
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• pp.566-572
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• 1997

유전자 치료등 폐암에 대한 새로운 치료법의 개발및 그 효능의 검증에 있어 적절한 동물 모델이 없음은 큰 제 한점중의 하나이다. 특히 종양의 생물학적 특성이나 치료에의 효과등이 장기자체의 환경에 크게 영향 을 받는다는 사실은, 인체에서의 폐암의 특성을 가지며 폐에 정 위적으로 발생하는 폐암의 동물모델의 개발 을 시급하게 한다. 저자등은 Nude rat을 대상 동물로 하여, 개흉하에 종양세포 부유액을 원하는 폐말단 부위에 직접 주입함으로 폐에 정 위적으로 폐암의 발달을 유도하였으며 이를 이용하여 발생된 비소세포 폐암의 병태를 연구하였다. 종양은 실험 대상 등물에서 모두 발생하였으며 이용한 두 가지 종류의 세포주(NCI-H46O과 NCI-H1299)에서 모두 효과적으로 발생하였다. 발생된 폐종양은 시간 경과에 따라 주위 조직으로의 침윤과 종격동 전이의 양상를 보였다. 종양 숙주 동물의 평균 수명은 약 5주 정도였다. 저자등이 개발한 비소세포폐암의 동물 모델은 기관지를 통한 종양 세포 주입법에 의한 폐암 모델에 비해 국소적으로 진행된 폐암을 원하는 부위에 정확히 만들 수 있음은 물론 외과적 처치를 비롯한 국소적 치료 방법의 개발이나 ?과의 검증에 두루 이용되기에 적절하다고 사료된다.