• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4147-4156
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• 2015

Lung cancer is a serious health problem and leading cause of death worldwide due to its high incidence and mortality. More than 80% of lung cancers feature a non-small cell histology. Over few decades, systemic chemotherapy and surgery are the only treatment options in this type of tumor but due to their limited efficacy and overall poor survival of patients, there is an urge to develop newer therapeutic strategies which circumvent the problems. Enhanced knowledge of translational science and molecular biology have revealed that lung tumors carry diverse driver gene mutations and adopt different intracellular pathways leading to carcinogenesis. Hence, the development of targeted agents against molecular subgroups harboring critical mutations is an attractive approach for therapeutic treatment. Targeted therapies are clearly more preferred nowadays over systemic therapies because they target tumor specific molecules resulting with enhanced activity and reduced toxicity to normal tissues. Thus, this review encompasses comprehensive updates on targeted therapies for the driver mutations in non-small cell lung cancer (NSCLC) and the potential challenges of acquired drug resistance faced i n the field of targeted therapy along with the imminent newer treatment modalities against lung cancer.

• Preventive Nutrition and Food Science
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• v.9 no.1
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• pp.65-70
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• 2004

Side-stream cigarette smoke (SSCS) is a major component of environmental tobacco smoke. The purpose of this study was to investigate the development of lung injury and lipid peroxidation in the lung and liver of immunodeficient (Nude) mice exposed to acute SSCS (a total 5 hours of exposure). The effects of French maritime bark extract (Pycnogeno $l^{ⓡ}$) supplementation of the mice were also determined. SSCS increased pulmonary resistance and lipid peroxidation in these mice. Pycnogeno $l^{ⓡ}$ supplementation increased vitamin E levels in lung and liver. In addition, Pycnogeno $l^{ⓡ}$ attenuated SSCS-mediated lung injury and lipid peroxidation. It appears that the enhanced resistance against SSCS-induced lung injury and lipid peroxidation may be primarily due to the antioxidant property of Pycnogeno $l^{ⓡ}$ in supplemented mice.

• Archives of Pharmacal Research
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• v.29 no.8
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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.

• Oncology Letters
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• v.41 no.6
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• pp.3305-3312
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• 2019

Histone H2B monoubiquitination has been shown to play critical roles in diverse cellular processes including DNA damage response. Although recent data indicate that H2B monoubiquitination is strongly connected with tumor progression and regulation, the implications of this modification in lung adenocarcinoma are relatively unknown. In the present study, we demonstrated the clinical implication of H2B monoubiquitination and the potential role of tumor necrosis factor receptor-associated factor-interacting protein (TRAIP) in regulating its modification in lung adenocarcinoma. Immunohistochemical analysis showed that H2B monoubiquitination was significantly downregulated in 68 human lung adenocarcinoma patient samples compared to their normal adjacent tissues. Depletion of TRAIP by specific siRNA treatment markedly decreased ionizing radiation (IR)-induced H2B monoubiquitination. In addition, deletion mutants without RING domain or C-terminus of TRAIP diminished the ability to induce H2B monoubiquitination at lysine 120. Notably, the nuclear expression of TRAIP was positively related with H2B monoubiquitination levels in patients with lung adenocarcinoma. Furthermore, statistical analysis indicated that low levels of both TRAIP and H2B monoubiquitination, not each alone, in patients with lung adenocarcinoma were strongly correlated with poor survival. Taken together, these results suggest that TRAIP is a novel regulator of H2B monoubiquitination in DNA damage response and cancer development in lung adenocarcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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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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• v.50 no.6
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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.

• Korean Journal of Veterinary Service
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• v.20 no.1
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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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• v.15 no.9
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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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• v.17 no.8
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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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• v.74 no.3
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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.