• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5237-5242
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• 2013

Background: Inflammation is a critical component of tumor progression. Many cancers arise from sites of infection, chronic irritation, and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an essential participant in the neoplastic process, promoting proliferation, survival and migration. Platelets can release some growth factors such as platelet-derived growth factor, platelet factor 4, and thrombospondin. Such factors have been shown to promote hematogenous tumour spread, tumor cell adhesion and invasion, and angiogenesis and to play an important role in tumor progression. In this study, we aimed to investigate effects of the pretreatment neutrophil to lymphocyte ratio (NLR) and the platelet to lymphocyte ratio (PLR) on survival and response to chemoradiotherapy in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: Ninety-four patients with non-metastatic NSCLC were included and separated into two groups according to median valuse of NLR and PLR (low:<3.44 or high:${\geq}3.44$ and low:<194 or high${\geq}194$, respectively). Results: Pretreatment high NLR and PLR were associated with significantly shorter disease-free and overall survival rates. Multivariate analysis revealed that the overall survival rates were significantly linked with PLR (OR: 1.87, CI: 1.20-2.91, p: 0.006) and response to chemoradiotherapy (OR: 1.80, CI: 1.14-2.81, p: 0.012) and the disease-free survival rates were significantly associated with NLR (OR: 1.81, CI: 1.16-2.82, p: 0.009) and response to chemoradiotherapy (OR: 2.30, CI: 1.45-3.66, p: 0.001). There was no significant difference between patients with high and low NLR in terms of response to chemoradiotherapy. Similarly, there was no significant influence of the PLR. Conclusions: Pretreatment NLR and PLR measurements can provide important prognostic results in patients with NSCLC and assessment of the two parameters together appears to better predict the prognosis in patients with NSCLC. The effect of inflammation, indicators of NLR and PLR, on survival seems independent of the response to chemoradiotherapy.

• Korean Journal of Head & Neck Oncology
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• v.27 no.1
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• pp.59-65
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• 2011

Background and Objectives : Papillary thyroid carcinoma(PTC) frequently metastasize to the regional neck, however, lateral neck lymph node metastasis is less common. The aim of this study is to investigate clinical and immunohistochemical features of PTC with lateral LN metastasis, and determine the predictive factors for lateral LN metastases. Material and Methods : We undertook a retrospective study of 83 patients treated between January 2007 and December 2009 for PTC by thyroidectomy with or without lateral neck dissection. The following criteria were used to study the clinical predictive value of lateral LN. metastases : sex, age, tumor size, multifocality, extracapsular spread(ECS) and lymphovascular emboli. Immunohistochemical staining for VEGF-A, VEGF-C, Bax, Bcl-2, Cyclin D1, Cyclin E, $p27^{kip1}$ and $p57^{kip2}$ was performed, and quantified blindly by three pathologists who had no clinical information of the patients. Immunohistochemical expression was scored as high(>50% of cells stained) or low(0-49%). Results : With use of univariate and multivariate analysis, tumor size(>2cm) and ECS were independent correlates of lateral LN metastasis in PTC. Expression of VEGF-C, Bax, and Cyclin D1 in the PTC with lateral LN metastasis was scored higher than in PTC without lateral LN metastasis(p<0.05). Conclusion : The important risk factors for lateral LN metastasis in PTC are primary tumor size and the presence of ECS. And expression of VEGF-C, Bax and cyclin D1 may be considered of lateral LN metastatic potential in PTC.

• The Journal of the Korean Society for Microbiology
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• v.14 no.1
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• pp.89-97
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• 1979

Nonspecific suppressions of the immune responses have been reported to occur in the cancer-bearing patients. The mechanisms responsible for these immunosuppressions remain unclear but some investigators suggested that the immunosuppressions may result from immunosuppressive factors exudated from tumor masses. This study was undertaken to evaluate the in vivo effects of ascitic and pleural fluids from patients with cancers metastatic to peritoneum or pleura on the immune responses of mice. Non-cancerous ascitic and pleural effusions were used as controls. The ascitic fluids from hepatomap atients and pleural fluids from pulmonary carcinoma patients decreased both the delayed-type hypersensitivity and the antibody formation only when these were injected before antigenic stimulation. Control effusions exerted no effect on the immune responses to mice. These results suggested that cancerous fluids suppressed the immune responses by affecting the afferent arc of the immune system.

• Korean Journal of Head & Neck Oncology
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• v.30 no.2
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• pp.53-61
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• 2014

Background and Objectives : Anaplastic thyroid carcinoma(ATC) is a rare but highly aggressive thyroid malignancy that is associated with an extremely poor survival despite the best multidisciplinary care. BRAF(V600E) mutation is detected in about a quarter of ATC, but unlike its high treatment response to selective BRAF inhibitor (PLX4032) in metastatic melanoma, the treatment response of ATC is reported to be low. The purpose of this study is to investigate the innate resistance mechanism responsible for this low treatment response to BRAF inhibitor and its effect on epithelial-mesenchymal transition(EMT). Materials and Methods : Two ATP cell lines, 8505C and FRO were selected and treated with PLX4032 and its drug sensitivity and effects on cell migration and EMT were examined and compared. Further investigation on the changes in signals responsible for the different treatment response to PLX4032 was carried out and the same experiment was performed on both orthotopic and ectopic xenograft mouse models. Results : FRO cell line was more sensitive to PLX4032 treatment compared to 8505C cell line. The resistance to BRAF inhibition in 8505C was due to increased expression of EGFR. Effective inhibition of both EGFR and p-AKT was achieved after dual treatment with BRAF inhibitor(PLX4032) and EGFR inhibitor(Erlotinib). Similar results were confirmed on in vivo study. Conclusion : EGFR-mediated reactivation of the PI3K/AKT pathway and MAPK pathway contributes to the relative insensitivity of BRAF(V600E) mutant ATC cells to PLX4032. Dual inhibition of BRAF and EGFR leads to sustained treatment response including cell invasiveness.

• Journal of Life Science
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• v.25 no.5
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• pp.607-614
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• 2015

Cancers are the largest cause of mortality and morbidity all over the world. Cordycepin, an adenosine analog, is a major functional component of the Cordyceps species, which has been widely used in traditional Oriental medicine. Over the last decade, this compound has been reported to possess many pharmacological properties, such as an ability to enhance immune function, as well as anti-inflammatory, antioxidant and anti-cancer effects. Recently, numerous studies have reported interesting properties of cordycepin as a chemopreventive agent as well. There is an accumulating body of experimental evidences suggesting that cordycepin impedes cancer progression by promoting apoptosis, inducing cell cycle arrest, modulating intracellular signaling pathways, and inhibiting invasion and metastasis of cancer cells. In many cancer cell lines, cordycepin inhibits growth and cell cycle progression by inducing arrest of the G2/M phase, resulting from the inhibition of retinoblastoma protein phosphorylation and induction of cyclin-dependent kinase inhibitors. To induce apoptosis, cordycepin activates the extrinsic and intrinsic pathways, which promotes reactive oxygen species generation and the downstream activation of kinase cascades. Cordycepin also can activate alternative pathways to cell death such autophagy. In addition, cordycepin can inhibit the pro-metastatic processes of cancer cell detachment, migration, and invasion through a variety of mechanisms, including the nuclear factor-kappa B and activated protein-1 signaling pathways. In this review, we summarized the variety of action mechanisms by which cordycepin may mediate chemopreventive effects on cancer and discussed the potential of this natural product as a promising therapeutic inhibitor of cancer development.

• Tuberculosis and Respiratory Diseases
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• v.64 no.5
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• pp.374-378
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• 2008

Angiosarcoma is a rare but highly malignant tumorthat usually arises in the scalp or face of elderly males. Distant metastases favor the lung, liver, lymph nodes and skin. Metastatic pulmonary angiosarcoma commonly takes the form of a nodule but can sometimes appear as a thin-walled cyst. We report a case of 65 years-old male with a spontaneous pneumothorax, who underwent excision and radiotherapy for an angiosarcoma of the scalp 2 years ago. A chest CT scan revealed multiple cysts in the lung. The video-assisted thoracoscopic lung biopsy demonstrated subpleural cysts without tumor cells. A skin biopsy of the scalp showed an angiosarcoma. This case was diagnosed as a recurrence of an angiosarcoma with a supposed lung metastasis. This case suggests that a spontaneous pneumothorax in elderly people may be secondary to a pulmonary metastasis from an angiosarcoma of the scalp.

• Molecules and Cells
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• v.41 no.6
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• pp.523-531
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• 2018

Tumour metastasis is one of the most serious challenges of cancer as it is the major cause of mortality in patients with solid tumours, including osteosarcoma (OS). In this regard, anti-metastatic genes have potential for metastasis inhibition strategies. Recent evidence showed the importance of breast cancer metastasis suppressor 1 (BRMS1) in control of OS invasiveness, but the regulation of BRMS1 in OS remains largely unknown. Here, we used bioinformatics analyses to predict BRMS1-targeting microRNAs (miRNAs), and the functional binding of miRNAs to BRMS1 mRNA was evaluated using a dual luciferase reporter assay. Among all BRMS1-targeting miRNAs, only miR-151b, miR-7-5p and miR-3200-5p showed significant expression in OS specimens. Specifically, we found that only miR-3200-5p significantly inhibited protein translation of BRMS1 via pairing to the 3'-UTR of the BRMS1 mRNA. Moreover, we detected significantly lower BRMS1 and significantly higher miR-3200-5p in the OS specimens compared to the paired adjacent non-tumour bone tissues. Furthermore, BRMS1 and miR-3200-5p levels were inversely correlated to each other. Low BRMS1 was correlated with metastasis and poor patient survival. In vitro, overexpression of miR-3200-5p significantly decreased BRMS1 levels and promoted OS cell invasion and migration, while depletion of miR-3200-5p significantly increased BRMS1 levels and inhibited OS cell invasion and migration. Thus, our study revealed that miR-3200-5p may be a critical regulator of OS cell invasiveness.

• Journal of Life Science
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• v.32 no.1
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• pp.51-55
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• 2022

Matrix metalloproteinase (MMP) enzymes are responsible for the degradation and formation of the extracellular matrix (ECM), and overproduction of MMPs is observed in several diseases, such as cancer and asthma, that progress with metastatic characteristics. Natural products, especially phytochemicals, have been an important source of MMP inhibitors with reduced side effects. Although the majority of phytochemicals inhibit the enzymatic activity of MMPs, some suppress MMP production. In this context, the current study evaluated the potential of Corydalis heterocarpa, a halophyte with reported bioactivities, to inhibit MMP expression in PMA-stimulated HT-1080 cells. A crude C. heterocarpa extract was shown to decrease the mRNA and protein expression of MMP-2 and MMP-9 while increasing the endogenous MMP inhibitors TIMP-1 and TIMP-2 which regulate MMP expression in healthy tissues. In addition, our results show that the inhibitory effects of C. heterocarpa might occur through suppression of the phosphorylation of MAPK signaling, the upstream activator of MMP overexpression. In conclusion, C. heterocarpa is a potential source of antimetastatic compounds that might serve as lead molecules to develop novel MMP inhibitors.

• Journal of the Korean Orthopaedic Association
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• v.54 no.5
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• pp.440-446
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• 2019

Purpose: This study assessed the treatment outcomes of myxoid liposarcoma in the extremities and investigate the prognostic factors. Materials and Methods: A total of 91 patients with myxoid liposarcoma (83 primary, 8 recurrent) between 2001 and 2015 were reviewed retrospectively. The local recurrence and metastasis after treatment were examined. The survival rates and prognostic factors affecting the survival were investigated. The mean follow-up was 84 months (range, 5-196 months). Results: The overall survival rates at 5-yr and 10-yr were 82% and 74%, respectively. The tumor size (p=0.04), round cell component (p<0.0001), grade (p=0.0002), and local recurrence (p=0.006) affected survival in primary patients. Extrapulmonary metastases were observed in 75.0% (18/24) of metastatic patients and the mean post metastasis survival was 26 months (range, 2-72 months) Conclusion: Myxoid liposarcoma developed mainly at the lower extremities. The tumor size, grade, component of round cells, and local recurrence were associated with the prognosis. The unique feature of extrapulmonary metastasis in myxoid liposarcoma should be noted in the treatment and follow-up.

• Radiation Oncology Journal
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• v.19 no.2
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• pp.171-180
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• 2001

Purpose : Expression of TIMP, intrinsic inhibitor of MMP, is regulated by signal transduction in response to genotoxins and is likely to be an important step in metastasis, angiogenesis and wound healing after ionizing radiation. Therefore, we studied radiation mediated TIMP expression and its mechanism in head and neck cancer cell lines. Materials and Methods : Human head and neck cancer cell lines established at Asan Medical Center were used and radiosensitivity $(D_0)$, radiation cytotoxicity and metastatic potential were measured by clonogenic assay, n assay and invasion assay, respectively. The conditioned medium was prepared at 24 hours and 48 hours after 2 Gy and 10 Gy irradiation and expression of TIMP protein was measured by Elisa assay with specific antibodies against human TIMP. hTIMP1 promoter region was cloned and TIMP1 luciferase reporter vector was constructed. The reporter vector was transfected to AMC-HN-1 and -HN-9 cells with or without expression vector Ras, then the cells were exposed to radiation or PMA, PKC activator. EMSA was peformed with oligonucleotide (-59/-53 element and SP1) of TIMP1 promoter. Results : $D_0$ of HN-1, -2, -3, -5 and -9 cell lines were 1.55 Gy, 1.8 Gy, 1.5 Gt, 1.55 Gy and 2.45 Gy respectively. n assay confirmed cell viability, over $94\%$ at 24hrs, 48hrs after 2 Gy irradiation and over 73% after 10 Gy irradiation. Elisa assay confirmed that cells secreted TIMP1, 2 proteins continuously. After 2 Gy irradiation, TIMP2 secretion was decreased at 24hrs in HN-1 and HN-9 cell lines but after 10 Gy irradiation, it was increased in all cell lines. At 48hrs after irradiation, it was increased in HN-1 but decreased in HN-9 cells. But the change in TIMP secretion by RT was mild. The transcription of TIMP1 gene in HN-1 was induced by PMA but in HN-9 cell lines, it was suppressed. Wild type Ras induced the TIMP-1 transcription by 20 fold and 4 fold in HN-1 and HN-9 respectively. The binding activity to -59/-53, AP1 motif was increased by RT, but not to SP1 motif in both cell lines. Conclusions : We observed the difference of expression and activity of TIMPs between radiosensitive and radioresistant cell line and the different signal transduction pathway between in these cell lines may contribute the different radiosensitivity. Further research to investigate the radiation response and its signal pathway of TIMPs is needed.