• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3625-3630
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• 2013

Reactive oxygen species (ROS) are known to promote mesothelial carcinogenesis that is closely associated with asbestos fibers and inflammation. Epithelial to mesenchymal cell transition (EMT) is an important process involved in the progression of tumors, providing cancer cells with aggressiveness. The present study was performed to determine if EMT is induced by $H_2O_2$ in human malignant mesothelioma (HMM) cells. Cultured HMM cells were treated with $H_2O_2$, followed by measuring expression levels of EMT-related genes and proteins. Immunohistochemically, TWIST1 expression was confined to sarcomatous cells in HMM tissues, but not in epithelioid cells. Treatment of HMM cells with $H_2O_2$ promoted EMT, as indicated by increased expression levels of vimentin, SLUG and TWIST1, and decreased E-cadherin expression. Expression of stemness genes such as OCT4, SOX2 and NANOG was also significantly increased by treatment of HMM cells with $H_2O_2$. Alteration of these genes was mediated via activation of hypoxia inducible factor 1 alpha (HIF-$1{\alpha}$) and transforming growth factor beta 1 (TGF-${\beta}1$). Considering that treatment with $H_2O_2$ results in excess ROS, the present study suggests that oxidative stress may play a critical role in HMM carcinogenesis by promoting EMT processes and enhancing the expression of stemness genes.

• Korean Journal of Head & Neck Oncology
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• v.18 no.2
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• pp.135-141
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• 2002

Backgrounds and Objectives: Metastasis is a complex multistep process that requires sequential interactions between the invasive cell and the extra-cellular matrix. Transforming growth factor-${\beta}1$ ($TGF-{\beta}1$) is a multifunctional regulator of cellular differentiation, motility and growth. Loss of sensitivity to the growth inhibitory effects by $TGF-{\beta}1$ plays important roles in neoplastic progression. The aim of this study was to investigate the role of $TGF-{\beta}1$ in the neoplastic invasion and metastasis through matrix metalloproteinase (MMP) of laryngeal cancer cell lines. Material and Methods: Two laryngeal cancer cell lines, SNU-899 and SNU-1076 were treated with recombinant $TGF-{\beta}1$, and the expression of MMP-2 and MMP-9 was immunohistochemically evaluated and gelatinase activity was studied by gelatin zymogram. Results: The cell growth inhibition was evident on 4th days after 1ng/ml and 10ng/ml $TGF-{\beta}1$ treatment. The expressions of MMP-2 and MMP-9, and their gelatinase activities were increased in dose-dependent manner. Conclusion: $TGF-{\beta}1$ treatment in laryngeal cancer cell lines induces the expression of MMP-2 and MMP-9, thus playing a role in the digestion of extracellular matrix gelatin.

• Molecular & Cellular Toxicology
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• v.3 no.4
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• pp.262-266
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• 2007

ENPP2, a 125 kDa secreted lysophopholipase D which originally identified as a tumor-motogen, Autotaxin, enhances cellular locomotion, cell proliferation, angiogenesis and cell survival by generating the signal molecule lysophosphatic acid or sphingosine-1-phosphate. Previous studies have suggested that expression of Autotaxin is associated with invasive phenotype in advanced breast carcinomas. Thus, to determine whether genetic alterations of ENPP2 gene are involved in the development or progression of breast cancer, we analyzed its somatic mutation in 85 breast carcinomas by single-stranded conformational polymorphism and sequencing. Overall, six ENPP2 mutations were found (7.0%), comprising five missense and one nonsense mutation (s). To our knowledge, this is the first report on ENPP2 mutation in breast carcinoma, and the data indicate that ENPP2 is occasionally mutated in breast carcinomas, and suggest that ENPP2 mutation may contribute to the tumor development in some breast carcinomas.

• Tuberculosis and Respiratory Diseases
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• v.75 no.3
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• pp.104-110
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• 2013

Background: Osteopontin (OPN) and carbonic anhydrase IX (CAIX), which are expressed on the surface of tumor cells, are associated with hypoxia during tumor development and progression. However, the roles of these proteins in the plasma of patients with non-small cell lung cancer (NSCLC) are poorly understood. Herein, we hypothesized that plasma OPN and CAIX levels could be used as diagnostic and prognostic tumor markers in patients with NSCLC. Methods: Fifty-three patients with NSCLC and 50 healthy control subjects were enrolled. We selected controls without malignancy and matched them with NSCLC patient cases according to age and gender. Blood samples were collected at the time of diagnosis; the plasma levels of OPN and CAIX were measured by enzyme-linked immunosorbent assays. Results: The plasma levels of OPN in the patients with NSCLC were significantly elevated as compared to those in the controls (p=0.016). However, there was no difference in the plasma level of CAIX between the NSCLC patients and controls. NSCLC patients with a distant metastasis had a remarkable increase in plasma OPN compared with patients without metastasis (p=0.026), but no such correlation was found for CAIX. There was no difference in overall survival rates according to the plasma level of OPN between the two groups (by Kaplan-Meier survival analysis). Conclusion: Plasma OPN levels were elevated in patients with NSCLC as compared with the controls, with greater elevation of OPN levels in the advanced stages of disease. Therefore, plasma OPN may have utility as a diagnostic, but not prognostic, biomarker of advanced NSCLC.

• Tuberculosis and Respiratory Diseases
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• v.79 no.4
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• pp.274-281
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• 2016

Background: Factors associated with the prognosis of patients with small cell lung cancer (SCLC) is relatively unknown, than of those with non-small cell lung cancer. This study was undertaken to identify the prognostic factors of SCLC. Methods: The medical records of 333 patients diagnosed with SCLC at tertiary hospital from January 1, 2008, to December 31, 2012 were retrospectively reviewed. Patients were categorized by age (${\leq}65$ years vs. >65 years) and by extent of disease (limited disease [LD] vs extensive disease [ED]). Overall survival and progression free survival rates were determined. Factors associated with prognosis were calculated using Cox's proportional hazard regression model. Results: Most baseline characteristics were similar in the LD and ED groups. Eastern Cooperative Oncology Group (ECOG) performance status (PS), first chemotherapy regimen, and prophylactic cranial irradiation (PCI) differed significantly in patients with LD and ED. Mean ECOG PS was significantly lower (p<0.001), first-line chemotherapy with etoposide-cisplatin was more frequent than with etoposide-carboplatin (p<0.001), and PCI was performed more frequently (p=0.019) in LD-SCLC than in ED-SCLC. Prognosis in the LD group was better in younger (${\leq}65$ years) than in older (>65 years) patients, but prognosis in the ED group was unrelated to age. Conclusion: This study showed that overall survival (OS) was significantly improved in younger than in older patients with LD-SCLC. Univariate and multivariate analyses showed that age, PCI and the sum of cycles were significant predictors of OS in patients with LD-SCLC. However, prognosis in the ED group was unrelated to age.

• Tuberculosis and Respiratory Diseases
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• v.83 no.1
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• pp.51-60
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• 2020

Background: Programmed death-ligand 1 (PD-L1) expression is tested by immunohistochemistry (IHC)-22C3, SP263, and SP142. The aim of this study is to evaluate the correlation among the three methods of PD-L1 IHC in non-small cell lung cancer (NSCLC) and clinical significance of PD-L1 expression in lung adenocarcinoma with an epidermal growth factor receptor (EGFR)-tyrosine kinase domain mutation. Methods: The results of 230 patients who were pathologically confirmed as having NSCLC; tested using PD-L1 IHC 22C3, SP263, and SP142 methods; and evaluated via the peptide nucleic acid clamping method to confirm EGFR mutation, were analyzed in this study. Results: 164 patients underwent both the SP263 and 22C3 tests. There was a significant positive correlation between the outcomes of the two tests (Spearman correlation coefficient=0.912, p<0.001), with a derived regression equation as follows: 22C3=15.2+0.884×SP263 (R²=0.792, p<0.001). There was no relationship between the expression of PD-L1 and clinical parameters, including EGFR-tyrosine kinase inhibitor (TKI) mutation. The PD-L1 expression in patients treated with EGFR-TKI yielded a 2-month-shorter progression period than that in the PD-L1-negative group. However, this did not reach statistical significance (PD-L1<1% vs. PD-L1≥1%, 10 months vs. 8 months). Conclusion: The results of the 22C3 and those of SP263 methods were in good correlation with one another. Since the PD-L1 expression is not influenced by the EGFR mutation, it is necessary to perform a PD-L1 test to set the treatment direction in the patients with EGFR-mutant NSCLC.

• Parasites, Hosts and Diseases
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• v.58 no.3
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• pp.217-227
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• 2020

Trichomonas vaginalis causes inflammation of the prostate and has been detected in tissues of prostate cancers (PCa), prostatitis and benign prostatic hyperplasia. Obesity is a risk factor for PCa and causes a chronic subclinical inflammation. This chronic inflammation further exacerbates adipose tissue inflammation as results of migration and activation of macrophages. Macrophages are the most abundant immune cells in the PCa microenvironment. M2 macrophages, known as Tumor-Associated Macrophages, are involved in increasing cancer malignancy. In this study, conditioned medium (TCM) of PCa cells infected with live trichomonads contained chemokines that stimulated migration of the mouse preadipocytes (3T3-L1 cells). Conditioned medium of adipocytes incubated with TCM (ATCM) contained Th2 cytokines (IL-4, IL-13). Macrophage migration was stimulated by ATCM. In macrophages treated with ATCM, expression of M2 markers increased, while M1 markers decreased. Therefore, it is suggested that ATCM induces polarization of M0 to M2 macrophages. In addition, conditioned medium from the macrophages incubated with ATCM stimulates the proliferation and invasiveness of PCa. Our findings suggest that interaction between inflamed PCa treated with T. vaginalis and adipocytes causes M2 macrophage polarization, so contributing to the progression of PCa.

• Tuberculosis and Respiratory Diseases
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• v.69 no.4
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• pp.293-297
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• 2010

A 60-year-old man was diagnosed with stage IV squamous cell carcinoma of lung and treated with weekly doses of docetaxel and cisplatin. Tumor mass and mediastinal lymphadenopathy disappeared after 4.5 cycles of chemotherapy. At one week post final chemotherapy, the patients developed sudden shortness of breath. New, multifocal infiltrations developed on both lungs without definitive evidence of infection. Despite administration of broad spectrum antibiotics, the lung lesion did not improve, so bronchoalveolar lavage and computed tomography-guided lung biopsy were performed. The proportion of lymphocytes was increased markedly and histopathology revealed squamous cell carcinoma combined with bronchiolitis obliterans organizing pneumonia. After high dose corticosteroid therapy, dyspnea and the newly developed consolidation had decreased slightly. However, dyspnea and hypoxemia increased again because of aggravated lung cancer since chemotherapy had stopped. Chemotherapy couldn't be restarted due to the poor performance status of the patient. Later, patient died of respiratory failure from poor general condition and progression of lung cancer.

• Journal of Korean Neurosurgical Society
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• v.61 no.1
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• pp.60-65
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• 2018

Objective : Choroidal metastases (CMs) are the most common intraocular tumor. Management is mainly radiation therapy with goals of pain control and visual improvement. However, many radiation-related complications are reported. Since gamma knife radiosurgery (GKS) for CM was first reported in 1995, few cases have been reported. We report 7 cases of CMs treated with GKS. Methods : From April 2011 to November 2014, 7 patients with CM underwent GKS. Their median age at treatment was 64 years (range, 51-71 years). Four males and three females were treated. Lung cancer was the most common primary pathology, followed by renal cell carcinoma and stomach cancer. Four patients had multiple cerebral lesions and were treated simultaneously for choroidal lesions. The median marginal dose of 20 Gy (range, 15-25 Gy) was administered at the 50% isodose line. Results : Median follow-up period after GKS was 8 months (range, 2-38.3 months). Four patients expired due to underlying malignancy progression. Except for two patients who were not followed with magnetic resonance image after GKS, all patients showed size reduction in the treated lesions, but a new choroidal lesion appeared in one patient and one recurred. Six of seven patients reported subjectively improved visual symptoms. Visual acuity improved in 2 patients, and 2 were stable upon objective examination. One patient showed no improvement in visual acuity, but ocular pain was relieved; another patient showed improved vision and tumor remission, but visual deterioration recurred. Conclusion : GKS was shown to be safe and effective and should be considered for CM treatment.

• BMB Reports
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• v.44 no.9
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• pp.601-606
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• 2011

HMGB1 is associated with human cancers and is an activator of autophagy which mediates chemotherapy resistance. We here show that the mRNA levels of HMGB1 are high in leukemia cells and it is involved in the progression of childhood chronic myeloid leukemia (CML). HMGB1 decreases the sensitivity of human myeloid leukemia cells K562 to anti-cancer drug induced death through up-regulating the autophagy pathway, which is confirmed by the observation with an increase in fusion of autophagosomes and autophagolysosomes. When overexpressing HMGB1, both mRNA levels of Beclin-1, VSP34 and UVRAG which are key genes involved in mammalian autophagy and protein levels of p-Bcl-2 and LC3-II are increased. Luciferase assays document that over-expression of HMGB1 increases the transcriptional activity of JNK and ERK, which may be silenced by siRNA. The results suggest that HMGB1 regulates JNK and ERK required for autophagy, which provides a potential drug target for therapeutic interventions in childhood CML.