• BMB Reports
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• v.51 no.12
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• pp.648-653
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• 2018

Serine protease inhibitor Kazal type 1 (SPINK1) plays a role in protecting the pancreas against premature activation of trypsinogen and is involved in cancer progression. SPINK1 promoted LAC cells growth, migration, and invasion. Mechanistically, we found that SPINK1 promoted LAC cells migration and invasion via up-regulating matrix metalloproteinase 12 (MMP12). We observed that SPINK1 expression was only up-regulated in lung adenocarcinoma (LAC) tissues, and was an independent prognostic factor for poor survival. Our results indicate that SPINK1 might be a potential biomarker for LAC that promotes progression by MMP12.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.2
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• pp.131-141
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• 2023

Compelling evidence has demonstrated the critical role of circular RNAs (circRNAs) during lung adenocarcinoma (LUAD) progression. Herein, we explored a novel circRNA, circ_0129047, and detailed its mechanism of action. The expression of circ 0129047, microRNA-665 (miR-665), and protein tyrosine phosphatase receptor type B (PTPRB) in LUAD tissues and cells was determined using reverse transcription quantitative polymerase chain reaction and Western blotting. Cell Counting Kit8 and colony formation assays were conducted to detect LUAD cell proliferation, and western blotting was performed to quantify apoptosis-related proteins (Bcl2 and Bax). Luciferase reporter and RNA immunoprecipitation assays were used to validate the predicted interaction between miR-665 and circ_0129047 or PTPRB. A xenograft assay was used for the in vivo experiments. Circ_0129047 and PTPRB were downregulated in LUAD tissues and cells, whereas miR-665 expression was upregulated. Overexpression of circ_0129047 suppresses LUAD growth in vivo and in vitro. Circ_0129047 is the target of miR-665, and the miR-665 mimic ablated the antiproliferative and pro-apoptotic phenotypes of LUAD cells by circ_0129047 augmentation. MiR-665 targets the 3'UTR of PTPRB and downregulates PTPRB expression. PTPRB overexpression offsets the pro-proliferative potential of miR-665 in LUAD cells. Circ_0129047 sequestered miR-665 and upregulated PTPRB expression, thereby reducing LUAD progression, suggesting a promising approach for preventing LUAD.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7295-7300
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• 2013

Lung cancer is the most common cause of cancer-related death in the world. The main types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC), the latter including squamous cell carcinoma (SCC), adenocarcinoma and large cell carcinoma. NSCLCs account for about 80% of all lung cancer cases. Microcephalin (MCPH1), also called BRIT1 (BRCT-repeat inhibitor of hTERT expression), plays an important role in the maintenance of genomic stability. Recently, several studies have provided evidence that the expression of MCPH1 gene is decreased in several different types of human cancers. We evaluated the expression of protein MCPH1 in 188 lung cancer and 20 normal lung tissues by immunohistochemistry. Positive MCPH1 staining was found in all normal lung samples and only some cancerous tissues. MCPH1-positive cells were significantly lower in lung carcinoma compared with normal tissues. Furthermore, we firstly found that MCPH1 expression in lung adenocarcinoma is higher than its expression in squamous cell carcinoma. Change in MCPH1 protein expression may be associated with lung tumorigenesis and may be a useful biomarker for identification of pathological types of lung cancer.

• Bulletin of the Korean Chemical Society
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• v.22 no.4
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• pp.372-374
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• 2001

Three simple carboxamides incorporating the phenethylamine moiety have been isolated from strain XR-NC of a symbiotic bacterium Xenorhabdus nematophilus. Their structures were identified by spectroscopic data and synthesis. The compounds exhibited significant cytotoxicities against human cancer-cell line, viz. the gastric adenocarcinoma, colon adenocarcinoma and lung adenocarcinoma.

• Tuberculosis and Respiratory Diseases
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• v.75 no.6
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• pp.231-235
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• 2013

Knowledge of molecular pathogenesis of non-small cell lung cancer has increased remarkably and changed the principles of treatment, especially during the past decade. These advancements have been limited mainly to adenocarcinoma of the lung. Recently, genetic alterations in squamous cell lung cancer (SQCLC) have been detailed and positive results of clinical trials using agents targeting these changes have indicated the potential for improved treatment outcomes for SQCLC.

• Korean Journal of Veterinary Pathology
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• v.3 no.2
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• pp.77-82
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• 1999

Testicles of nine-week-old male CBA/J mice were X-ray irradiated (1 Gy or 2 Gy) and were mated one week later with untreated virgin 12-week-old females of the same strain. The 1-Gy offspring (88 males and 62 females), 2-Gy offspring (100 males and 93 females) and additional offs pring (83 males and 84 females) were treated once subcutaneously with 0.1 mg/g body weight of urethane at 6 weeks of age. These three groups of off offspring showed similar incidences of lung tumors in both sexes. Depending on the doses of paternal X-ray irradiation, increasing incidences of adenocarcinoma were observed in the male 1-Gy and 2-Gy offspring groups. An increased multiplicity of lung carcinomas was observed in the male 2-Gy progeny that was statistically significant when compared with the control group. The results indicate that prezygotic testicular X-ray exposure of patemal animals causes the shift of adenoma-carcinoma sequence towards malignancy in the progeny.

• Tuberculosis and Respiratory Diseases
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• v.43 no.2
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• pp.262-266
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• 1996

Intradural extramedullary spinal metastasis from systemic tumor is extremely rare but epidural extramedullary cord tumor metastasis from the lung is relatively common. A 57 year-old male patient was admitted to department of internal medicine and neurosurgery in Chonbuk National University Hospital because of coughing, low back pain radiate to the right great toe, and numbness of the right calf area. Spinal MRI scan revealed round oval shaped mass lesion on just below the level of the conus medullaris. Authors present the clinical, histologic, radiologic features of spinal intradural metastatic tumor and operative total removal followed by chemothrapy with an extensive review of literatures.

• Molecules and Cells
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• v.45 no.6
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• pp.376-387
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• 2022

Extracellular vesicles (EVs) play an essential role in the communication between cells and the tumor microenvironment. However, the effect of tumor-derived EVs on the growth and metastasis of lung adenocarcinoma (LUAD) remains to be explored. This study aimed to elucidate the role of miR-153-3p-EVs in the invasion and migration capabilities of LUAD cells and explore its mechanism through in vivo and in vitro experiments. We found that miR-153-3p was specifically and highly expressed in LUAD and its secreted EVs. Furthermore, the expression of BANCR was negatively regulated by miR-153-3p and identified as a target gene of miR-153-3p using luciferase reporter assays. Through further investigation, we found that the downregulation of BANCR activates the PI3K/AKT pathway and accelerates the process of epithelial-mesenchymal transition (EMT), which ultimately leads to the aggravation of LUAD. The orthotopic xenograft mouse model was established to illustrate the effect of miR-153-3p-EVs on LUAD. Animal studies showed that miR-153-3p-EVs accelerated tumor growth in mice. Besides, we found that miR-153-3p-EVs could damage the respiratory ability of mice and produce a mass of inflammatory cells around the lung tissue of mice. Nevertheless, antagomir-153-3p treatment could inhibit the deterioration of respiratory function and inhibit the growth of lung tumors in mice. In conclusion, our study reveals the potential molecular mechanism of miR-153-3p-EVs in the development of LUAD and provides a potential strategy for the treatment of LUAD.

• Molecules and Cells
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• v.41 no.8
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• pp.733-741
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• 2018

Mutations in spliceosome components have been implicated in carcinogenesis of various types of cancer. One of the most frequently found is U2AF1 S34F missense mutation. Functional analyses of this mutation have been largely limited to hematological malignancies although the mutation is also frequently seen in other cancer types including lung adenocarcinoma (LUAD). We examined the impact of knockdown (KD) of wild type (wt) U2AF1 and ectopic expression of two splice variant S34F mutant proteins in terms of alternative splicing (AS) pattern and cell cycle progression in A549 lung cancer cells. We demonstrate that induction of distinct AS events and disruption of mitosis at distinct sub-stages result from KD and ectopic expression of the mutant proteins. Importantly, when compared with the splicing pattern seen in LUAD patients with U2AF1 S34F mutation, ectopic expression of S34F mutants but not KD was shown to result in common AS events in several genes involved in cell cycle progression. Our study thus points to an active role of U2AF1 S34F mutant protein in inducing cell cycle dysregulation and mitotic stress. In addition, alternatively spliced genes which we describe here may represent novel potential markers of lung cancer development.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6663-6667
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• 2013

Purpose: The current research was conducted to investigate the efficacy and safety of pemetrexed given continuously as a basement agent for first-, second- to third line chemotherapy of patients with metastatic lung adenocarcinoma. Patients and Methods: Patients with metastatic lung adenocarcinoma who were diagnosed in Jiangsu Cancer Hospital and Research Insitute, were enrolled. All received pemetrexed 500 $mg/m^2$ (intravenous; on day 1), and another chemotherapieutic agent every 3 weeks until disease progression, or intolerable toxicity. Then the patients were changed to a second line chemotherapy that was still based on pemetrexed 500 $mg/m^2$ and another chemotherapeutic agent differing from the first line example, until disease progression, or intolerable toxicity. When third line chemotherapy was needed, pemetrexed 500 $mg/m^2$ and another new chemotherapeutic agent were combined until disease progression. Evaluation of efficacy was conducted after two cycles of chemotherapy using the Response Evaluation Criteria for Solid Tumors. Toxicity was recorded according to NCI Criteria for Adverse Events version 3.0. Results: From January 2010 to September 2013, 15 patients were enrolled. Their median age was 56 years (range 43 to 77 years). Eight patients were male and 7 female. Five patients (33.3%) achieved PR, while 6 patients (40.0%) remained stable, no CR on first line; and 1 PR (7.7%), 5 stable (38.5%) were recorded when pemetrexed was ordered in second line; 5 patients (41.7%) were stable after pemetrexed was combined in third line; no complete response was observed. Main side effects were grade 1 to 2 neutrophil suppression and thrombocytopenia. Other toxicities included elevated transaminase and oral mucositis, but no treatment related death occurred. Conclusions: Pemetrexed continuously as a basement agent from first-, second- to third line chemotherapy is mildly effective in treating patients with metastatic lung adenocarcinoma with tolerable toxicity.