• BMB Reports
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• v.50 no.5
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• pp.233-234
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• 2017

Aberrant expression of the polypeptide N-acetyl-galactosaminyltransferase (GALNTs) has been associated with cancer, but their function(s) in metastasis remains elusive. We have recently identified GALNT14, one of the O-GalNAc glycosylation-initiating enzymes, as a prognostic marker for pulmonary relapse in breast cancer patients. Furthermore, we showed that GALNT14 promotes lung metastasis by the following novel mechanisms: 1) enhancing metastasis initiation by inhibiting the anti-metastatic effect of BMP produced from the lung stroma, 2) exploiting growth signals (e.g. FGF) supplied by macrophages, for their growth into macrometastases in the lung environment. These multi-faceted roles of GALNT14 in lung metastasis are achieved by GALNT14-mediated inhibition and activation of the BMP and FGF signaling pathways, respectively. The link among GALNT14, its downstream pathways and lung metastasis, provides us with an opportunity to develop effective therapeutic intervention for breast cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.1833-1840
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• 2013

Metastasis is one of the hallmarks of malignant neoplasms and is the leading cause of death in many cancer patients. A major challenge in cancer treatment is to find better ways to specifically target tumor metastasis. In this study, the anti-metastatic potential of the methanolic extract of Rhizophora apiculata (R.apiculata) was evaluated using the B16F-10 melanoma induced lung metastasis model in C57BL/6 mice. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with R.apiculata extract (10 mg/kg b.wt (intraperitoneal) significantly (p<0.01) inhibited pulmonary tumor nodule formation (41.1 %) and also increased the life span (survival rate) 107.3 % of metastatic tumor bearing animals. The administration of R.apiculata extract significantly (p<0.01) reduced biochemical parameters such as lung collagen hydroxyproline, hexosamine, uronic acid content, serum nitric oxide (NO), ${\gamma}$-glutamyl transpeptidase (GGT) and sialic acid levels when compared to metastasis controls. These results correlated with lung histopathology analysis of R.apiculata extract treated mice showing reduction in lung metastasis and tumor masses. Taken together, our findings support that R.apiculata extract could be used as a potential anti-metastasis agent against lung cancer.

• BMB Reports
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• v.49 no.11
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• pp.623-628
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• 2016

GPR78 is an orphan G-protein coupled receptor (GPCR) that is predominantly expressed in human brain tissues. Currently, the function of GPR78 is unknown. This study revealed that GPR78 was expressed in lung cancer cells and functioned as a novel regulator of lung cancer cell migration and metastasis. We found that knockdown of GPR78 in lung cancer cells suppressed cell migration. Moreover, GPR78 modulated the formation of actin stress fibers in A549 cells, in a RhoA- and Rac1-dependent manner. At the molecular level, GPR78 regulated cell motility through the activation of $G{\alpha}q$-RhoA/Rac1 pathway. We further demonstrated that in vivo, the knockdown of GPR78 inhibited lung cancer cell metastasis. These findings suggest that GPR78 is a novel regulator for lung cancer metastasis and may serve as a potential drug target against metastatic human lung cancer.

• Archives of Craniofacial Surgery
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• v.24 no.5
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• pp.240-243
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• 2023

Metastasis of lung cancer to the skin is uncommon, presenting in 0.22% to 12% of lung cancer patients, and it is extremely rare for skin metastasis to be the first clinical manifestation of lung cancer. In the few cases where skin metastasis has been reported as the first sign of lung cancer, the patients were typically heavy smokers or had preexisting respiratory diseases and symptoms. This prompted clinicians to consider skin metastasis of a pulmonary malignancy. Large cell neuroendocrine carcinoma (LCNEC) is a rare type of lung cancer that accounts for approximately 3% of lung cancers. LCNEC mainly metastasizes to visceral organs, such as the liver, bone, and brain, and it only shows metastasis to the skin in very rare cases. Herein, we report an unusual case of a metastatic skin lesion as the first sign of primary pulmonary LCNEC, in a 63-year-old woman with no pulmonary symptoms or personal history of smoking or pulmonary disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.15
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• pp.6369-6374
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• 2014

Lung cancer (LC) is the leading cause of cancer mortality worldwide, predominantly due to the difficulty of early diagnosis and its high metastatic potential. Recently, increasing evidence suggests that circulating tumour cells (CTCs) are responsible for cancer metastatic relapse, and CTCs have attracted interest in cancer metastasis detection and quantification. In present study, we collected blood samples from 67 patients with bone metastasis, and 30 patients without such metastasis, and searched for CTCs. Then the association of CTC numbers with bone metastasis and other clinico-pothological variants was analyzed. Results demonstrated that when 5 or 1 was taken as a threshhold for the CTC number, there were significantly higher positivity of CTCs in the bone metastasis group than in the non-metastasis group. While the increase in CTC number was not significantly associated with any other clinicopathological factor, including age, gender, pathological type, intrapulmonary metastasis and lymph node metastasis, the CTC number in patients with positivity of the last above mentioned variants was obviously higher than in patients with negativity of the two variants. Taken together, the CTC number appears to be significantly associated with the bone metastasis from lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.613-615
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• 2012

The aim of this study was to ana1yze T-cell lymphoma invasion and metastasis-inducing factor 1 (Tiam1) expression in 1ung cancer patients. A total of 204 patients with lung cancer tissue lesions were enrolled in the present study, along with 40 cases of normal lung tissue and 40 of normal fetal lung tissue. Tiam1 protein expression level was determined using intensity quantitative analysis, for comparison in lung cancer, metastatic, normal lung, and fetal lung tissue. The positive unit (PU) of Tiam1 was $13.5{\pm}5.42$ in lung cancer,$5.67{\pm}1.56$ in norma1 epithelial cells, and $5.89{\pm}1.45$ in fetal lung epithelial cells. The value in the lung cancer tissue was significantly higher than that in the normal lung tissue and the fetal lung tissue (P<0.01). The Tiam1 PU values with lymph node metastasis and without 1ymph node metastasis were $15.2{\pm}4.34$ and $12.5{\pm}4.23$, respectively, and the difference was statistically significant (P<0.05). The Tiam1 PU values in different tumor, nodes, metastasis (TNM) stages, III-IV period, and I-II phase were $14.7{\pm}4.14$ and $11.0{\pm}5.34$ (P<0.05). A correlation was found between Tiam1 expression and the age of patient, tumor size, tumor type, and tumor differentiation. Tiam1 protein expression in the lung tumor tissue is significantly higher than that in the normal lung tissue and fetal lung tissue. Tiam1 expression may be closely related to lung cancer development and metastasis.

• Tuberculosis and Respiratory Diseases
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• v.70 no.2
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• pp.139-142
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• 2011

Background: Lung cancer is responsible for substantial proportions of cutaneous metastasis from internal malignancies. The aim of this study was to evaluate the clinical manifestations and outcomes of cutaneous metastasis in Korean lung cancer patients. Methods: On a retrospective basis, we analyzed medical records of all patients diagnosed with lung cancer from 2000 to 2006. Results: Cutaneous metastases were found in 10 of 4,385 patients. The number of cases was highest for squamous cell carcinoma. However, there was no metastasis from 754 cases of small cell carcinomas. Cutaneous metastasis was detected during staging work-up in 4 patients and it was the presenting sign of recurrence post-operative in 2 patients. Average time from the diagnosis to discovery of cutaneous metastasis was 16.3 months and median survival was 8.5 months (range, 1.8~19.1 months). Conclusion: Physicians should be acquainted with clinical manifestations and outcomes of cutaneous metastasis from lung cancer to detect new, recurrent cancer, or disease progression, and to administer appropriate and prompt management.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.16
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• pp.6843-6848
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• 2014

Background: Diffusion-weighted magnetic resonance imaging (DWI) is reported to be useful for detecting malignant lesions. The purpose of this study is to clarify characteristics of imaging, detection rate and sensitivity of DWI for recurrence or metastasis of lung cancer. Methods: A total of 36 lung cancer patients with recurrence or metastasis were enrolled in this study. While 16 patients underwent magnetic resonance imaging (MRI), computed tomography (CT) and positron emission tomography-computed tomography (PET-CT), 17 underwent MRI and CT, and 3 underwent MRI and PET-CT. Results: Each recurrence or metastasis showed decreased diffusion, which was easily recognized in DWI. The detection rate for recurrence or metastasis was 100% (36/36) in DWI, 89% (17/19) in PET-CT and 82% (27/33) in CT. Detection rate of DWI was significantly higher than that of CT (p=0.0244) but not significantly higher than that of PET-CT (p=0.22). When the optimal cutoff value of the apparent diffusion coefficient value was set as $1.70{\times}10^{-3}mm^2/sec$, the sensitivity of DWI for diagnosing recurrence or metastasis of lung cancer was 95.6%. Conclusions: DWI is useful for detection of recurrence and metastasis of lung cancer.

• Tuberculosis and Respiratory Diseases
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• v.70 no.5
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• pp.423-427
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• 2011

Epithelioid sarcomas are rare soft tissue sarcomas with a high tumor grade and high local recurrence and metastasis rates. Although the lung is the most common site of metastasis, endobronchial metastasis hasn't been reported yet. We now report a case of epithelioid sarcoma with endobronchial metastasis. A 28-year-old man had recurrent pneumothorax and underwent wedge resection. He presented at our hospital with hemoptysis, dyspnea, and chest pain. Chest computed tomography revealed left pneumothorax, multiple lung nodules and endobronchial lesions at the right lower basal lobe. Bronchoscopy showed a hemorrhagic mass obstructing the bronchus of the right lower basal lobe. Magnetic resonance imaging revealed multiple nodular lesions in the left thigh muscles. The bronchoscopic biopsy of the endobronchial lesion and the muscle biopsy of the thigh showed the same feature epithelioid sarcoma. This is the first case report of an epithelioid sarcoma with endobronchial metastasis that was diagnosed by bronchoscopic biopsy.

• Journal of Microbiology and Biotechnology
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• v.10 no.3
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• pp.399-404
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• 2000

The adjuvant effect of a muramyl dipeptide (MDP) derivative, MDP-Lys(L18), on enhancing of antitumor immunity induced by X-irradiated tumor cells against highly metastatic B16-BL6 melanoma cells was examined in mice. Mice immunized intradermally (i.d.) with a mixture of X-irradiated B16-BL6 cells and MDP-Lys (L18) [Vac+MDP-Lys (L18)] followed by an intravenous (i.v.)inoculation of $10^4$ viable tumor cells 7 days after immunization, showed a significant inhibition of experimental lung metastasis of B16-BL6 melanoma cells. The most effective immunization for the prophylactic inhibition of tumor metastasis was obtained from the mixture of $100{\;}\mu\textrm{g}$ of MDP-Lys (L18) and $10^4$ X-irradiatied tumor vaccine. Furthermore, immunization of mice with Vac+MDP-Lys(L18), 3 days after tumor challenge, resulted in a significant inhibition of lung metastasis of B16-BL6 melanoma cells in an experimental lung metastasis model. Similarly, the administration of Vac+MDP-Lys(L18), 1 or 7 days after tumor removal, markedly inhibited tumor metastasis of B16-BL6 in a spontaneous lung metastasis model. When Vac+MDP-Lys (L18) was i.d. administered 3 days after subcutaneous (s.c.) inoculation of tumor cells ($5{\times}10^5/site$) on the back, mice treated with Vac+MDP-Lys(L18) showed inhibition of significantly tumor growth on day 20. These results suggest that MDP-Lys (L18) is able to enhance antitumor activity induced by X-irradiated tumor vaccine to reduce lung metastasis of tumor cells, and is a potent immunomodulating agent which may be applied prophylactically as well as therapeutically to treatment of cancer metastasis.