• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.4947-4951
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• 2012

Objective: Lung cancer is a deadly cancer, whose kills more people worldwide than any other malignancy. SLUG (SNAI2, Snail2) is involved in the epithelial mesenchymal transition in physiological and in pathological contexts and is implicated in the development and progression of lung cancer. Methods: We constructed a lentivirus vector with SLUG shRNA (LV-shSLUG). LV-shSLUG and a control lentivirus were infected into the non-small cell lung cancer cell A549 and real-time PCR, Western blot and IHC were applied to assess expression of the SLUG gene. Cell proliferation and migration were detected using MTT and clony formation methods. Results: Real-time PCR, Western Blot and IHC results confirmed down-regulation of SLUG expression by its shRNA by about 80%~90% at both the mRNA and protein levels. Knockdown of SLUG significantly suppressed lung cancer cell proliferation. Furthermore, knockdown of SLUG significantly inhibited lung cancer cell invasion and metastasis. Finally, knockdown of SLUG induced the down-regulation of Bcl-2 and up-regulation of E-cadherin. Conclusion: These results indicate that SLUG is a newly identified gene associated with lung cancer growth and metastasis. SLUG may serve as a new therapeutic target for the treatment of lung cancer in the future.

• The Korean Journal of Nuclear Medicine Technology
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• v.18 no.1
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• pp.26-32
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• 2014

Purpose: As PET-MRI which has excellent soft tissue contrast is developed as integration system, many researches about clinical application are being conducted by comparing with existing display equipments. Because PET-MRI is actively used for head and neck cancer diagnosis in our hospital, lymph node metastasis before the patient's surgery was diagnosed and clinical usefulness of head and neck cancer PET-MRI scan was evaluated using pathological opinions and idiopathy surrounding tissue metastasis evaluation method. Materials and Methods: Targeting 100 head and neck cancer patients in SNUH from January to August in 2013. $^{18}F-FDG$ (5.18 MBq/kg) was intravenous injected and after 60 min of rest, torso (body TIM coil, Vibe-Dixon) and dedication (head-neck TIM coil, UTE, Dotarem injection) scans were conducted using $Bio-graph^{TM}$ mMR 3T (SIEMENS, Munich). Data were reorganized using iterative reconstruction and lymph node metastasis was read with Syngo.Via workstation. Subsequently, pathological observations and diagnosis before-and-after surgery were examined with integrated medical information system (EMR, best-care) in SNUH. Patient's diagnostic information was entered in each category of $2{\times}2$ decision matrix and was classified into true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Based on these classified test results, sensitivity, specificity, accuracy, false negative and false positive rate were calculated. Results: In PET-MRI scan results of head and neck cancer patients, positive and negative cases of lymph node metastasis were 49 and 51 cases respectively and positive and negative lymph node metastasis through before-and-after surgery pathological results were 46 and 54 cases respectively. In both tests, TP which received positive lymph node metastasis were analyzed as 34 cases, FP which received positive lymph node metastasis in PET-MRI scan but received negative lymph node metastasis in pathological test were 4 cases, FN which received negative lymph node metastasis but received positive lymph node metastasis in pathological test was 1 case, and TN which received negative lymph node metastasis in both two tests were 50 cases. Based on these data, sensitivity in PET-MRI scan of head and neck cancer patient was identified to be 97.8%, specificity was 92.5%, accuracy was 95%, FN rate was 2.1% and FP rate was 7.00% respectively. Conclusion: PET-MRI which can apply the acquired functional information using high tissue contrast and various sequences was considered to be useful in determining the weapons before-and-after surgery in head and neck cancer diagnosis or in the evaluation of recurrence and remote detection of metastasis and uncertain idiopathy cervical lymph node metastasis. Additionally, clinical usefulness of PET-MRI through pathological test and integrated diagnosis and follow-up scan was considered to be sufficient as a standard diagnosis scan of head and neck cancer, and additional researches about the development of optimum MR sequence and clinical application are required.

• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.662-669
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• 2007

Objectives : The aim of the present study is to derive further studies evaluating the effectiveness of oriental medical treatment on colon cancer patients. We present a case of a patient diagnosed with colon cancer with colon cancer with liver metastasis who has survived more than 8 years. Methods : We followed all of treatments and examination. We prescribed the patient to take HangAm-dan(HAD) three times a day for 5 years and 1 month from January, 2000 to February, 2005. Abdominal computed tomography(CT) was performed to evaluate the therapeutic efficacy and measuring concentration of carcinoembryonic antigen(CEA) in blood serum was also performed to monitor therapeutic response. Results : The patient was diagnosed with liver metastasis in September of 1999 but has survived for over 8 years since. Abdomen CT show no interval change. Conclusions : This case may give us a possibility that oriental medical treatment offers potential benefits for patients with colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.167-174
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• 2014

Tumor angiogenesis, growth and metastasis are three closely related processes. We therefore investigated the effects of barbigerone on all three in the B16F10 tumor model established in both zebrafish and mouse models, and explored underlying molecular mechanisms. In vitro, barbigerone inhibited B16F10 cell proliferation, survival, migration and invasion and suppressed human umbilical vascular endothelial cell migration, invasion and tube formation in concentration-dependent manners. In the transgenic zebrafish model, treatment with $10{\mu}M$ barbigerone remarkably inhibited angiogenesis and tumor-associated angiogenesis by reducing blood vessel development more than 90%. In vivo, barbigerone significantly suppressed angiogenesis as measured by H and E staining of matrigel plugs and CD31 staining of B16F10 melanoma tumors in C57BL/6 mice. Furthermore, it exhibited highly potent activity at inhibiting tumor growth and metastasis to the lung of B16F10 melanoma cells injected into C57BL/6 mice. Western blotting revealed that barbigerone inhibited phosphorylation of AKT, FAK and MAPK family members, including ERK, JNK, and p38 MAPKs, in B16F10 cells mainly through the MEK3/6/p38 MAPK signaling pathway. These findings suggested for the first time that barbigerone could inhibit tumor-angiogenesis, tumor growth and lung metastasis via downregulation of the MEK3/6/p38 MAPK signaling pathway. The findings support further investigation of barbigerone as a potential anti-cancer drug.

• The Journal of Internal Korean Medicine
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• v.34 no.4
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• pp.466-477
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• 2013

Objectives : To report and demonstrate the effect of decreasing ascites volume by SB intraperitoneal injection to a refractory ascites patient with synchronous colorectal liver metastasis and metachronous peritoneal carcinomatosis. Methods : Two cycles of intraperitoneal and intravenous SB injection were conducted. Each injection cycle was made up of 4 days. Nine vials of SB were injected to the patient every day. To compare the volume of ascites between pret- and post-treatment, follow-up computed tomography was done on June 3, 2013. To observe other therapeutic effects of SB injection, laboratory tests were conducted periodically. Results : On the follow-up computed tomography images, the amount of ascites and pleural effusion had decreased compared to the April 30, 2013 computed tomography images. The levels of aspartate transaminase, alanine aminotransferase and lactate dehydrogenase decreased significantly from May 9, to May 30, 2013. The amount of oral intake increased constantly during hospitalization. The patient's symptoms such as abdominal distension, abdominal pain and dyspnea were improving until discharge. Conclusions : Even if thiese results cannot be applied to every synchronous colorectal cancer liver metastasis patient, we demonstrated that SB intraperitoneal injection has ascites-decreasing effect to refractory ascites patients with synchronous colorectal liver metastasis and metachronous peritoneal carcinomatosis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.2
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• pp.989-997
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• 2014

AMFR, autocrine motility factor receptor, also called gp78, is a cell surface cytokine receptor which has a dual role as an E3 ubiquitin ligase in endoplasmic reticulum-associated degradation. AMFR expression is associated with tumor malignancy. We here investigated the clinical significance of AMFR and its role in metastasis and prognosis in gastric cancer. Expression of AMFR, E-cadherin and N-cadherin in cancer tissues and matched adjacent normal tissues from 122 gastric cancer (GC) patients undergoing surgical resection was assessed by immunohistochemistry. Levels of these molecules in 17 cases selected randomly were also analysed by Western blotting. AMFR expression was significantly increased in gastric cancer tissues, and associated with invasion depth and lymph node metastasis. Kaplan-Meier analysis showed AMFR expression correlated with poor overall survival and an increased risk of recurrence in the GC cases. Cox regression analysis suggested AMFR to be an independent predictor for overall and recurrence-free survival. E-cadherin expression was decreased in gastric cancer tissues; conversely, N-cadherin was increased. Expression of AMFR negatively correlated with E-cadherin expression, whereas N-cadherin expression showed a significant positive correlation with AMFR expression. AMFR might be involved in the regulation of epithelial-mesenchymal transition, with aberrant expression correlating with a poor prognosis and promoting invasion and metastasis in GCs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.35 no.4
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• pp.213-220
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• 2009

Purpose: The present study was aimed to examine the usefulness of 18F-FDG PET/CT in the evaluation of cervical lymph node metastasis in patients with oral cancer. Materials and methods: Twenty-two patients who underwent neck dissection to treat oral cancer were subjected for examination. The cervical node metastasis was evaluated by means of clinical examination, CT scan, PET, and histologic examination. By comparing the results of each examination modality with those of histologic examination, it's sensitivity, specificity, positive predictive value, and negative predictive value were determined. Results: The oral cancer was more frequent in males with a ratio of 2.14:1. The sixth decade showed the highest incidence in age distribution with mean of $56{\pm}16$. Histologic findings showed that squamous cell carcinoma was the most common (15 patients), and mucoepidermoid carcinoma (3), malignant melanoma (2), and adenoid cystic carcinoma and ghost cell odontogenic carcinoma (1 each), in order. In most cases, wide surgical excision of the primary cancer and neck dissection was performed, followed by reconstruction with free flaps when necessary. When comparing the results of each examination modality with those of the histologic examination, clinical examination showed sensitivity, specificity, positive predictive value, and negative predictive value at 11%, 85%, 33%, and 58%, respectively. CT scans showed at 67%, 77%, 67%, and 77%, while $^{18}F$-FDG PET/CT at 78%, 77%, 70%, and 83%, respectively. Conclusions: These results suggest that PET is more useful, compared with clinical examination and CT scans, in the evaluation of cervical lymph node metastasis in patients with oral cancer.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.5
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• pp.391-396
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• 2014

Although interleukin-11 (IL-11) has been reported to be elevated in hypoxic tumors and has been associated with a poor prognosis in various cancers, little is known about its precise role in promoting metastasis in hypoxic tumors. In the present study, the molecular mechanism underlying the effects of IL-11 on MDA-MB-231 breast cancer cells migration and invasion in relation to metastasis under hypoxic conditions has been defined. Inhibition of IL-11 expression or function using small interfering RNA (siRNA) or a neutralizing antibody attenuated hypoxic MDA-MB-231 breast cancer cell migration and invasion through down-regulation of matrix metalloproteinases (MMPs) and activation of epithelial-to-mesenchymal transition (EMT) related gene expression. In addition, hypoxia-induced IL-11 increased STAT3 phosphorylation and STAT3 knockdown suppressed hypoxic MDA-MB-231 breast cancer cell invasion due to reduced MMP levels and reprogrammed EMT-related gene expression. These results suggest that one of the hypoxic metastasis pathways and the regulation of this pathway could be a potential target for novel cancer therapeutics.

• Journal of Gastric Cancer
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• v.15 no.2
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• pp.139-142
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• 2015

Hepatic metastasis of early gastric cancer (EGC) following subtotal gastrectomy with lymphadenectomy is rare. We report the case of a 61-year-old male patient who was diagnosed with EGC that was initially treated using endoscopic submucosal dissection (ESD) and subsequently underwent laparoscopic subtotal gastrectomy. Histopathological examination of the patient's ESD specimen showed a moderately differentiated tubular adenocarcinoma invading the submucosa without lymphatic invasion. The deep margin of the specimen was positive for adenocarcinoma, and he subsequently underwent laparoscopic distal gastrectomy. The patient developed liver metastasis 15 months after the operation and then underwent liver resection. Histology of the resected specimen confirmed the diagnosis of two foci of metastatic adenocarcinoma originating from stomach cancer. Immunohistochemical analysis of the specimen demonstrated overexpression of human epidermal growth factor receptor 2. The patient was treated with trastuzumab in combination with chemotherapy consisting of capecitabine and cisplatin. Twenty-four months after the operation, the patient remained free of recurrence.

• Biomedical Science Letters
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• v.17 no.1
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• pp.85-88
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• 2011

Tumor angiogenesis, which is essential for tumor growth and tumor metastasis, depends on angiogenic factors produced by tumor cells and/or infiltrating cells such as endothelial cells and immune cells in tumor tissue. Previously, we reported that licochalcone A (LicA), an important bioactive compound of Glycyrrhiza inflate, suppresses angiogenesis, tumor growth and metastasis. In this study, we evaluated the effect of LicA on angiogenin production in colon cancer cells because angiogenin is an essential factor to regulate angiogenesis and tumor progression. When we examined the angiogenin levels in three human colon cancer cells, HT-29, SW480 and Caco-2, LicA treatment significantly reduced the amounts of angiogenin among three cancer cell lines. In an in vivo study in which mice were implanted with HT-29 cells, oral administration of LicA reduced angiogenin in tumor tissues when compared with vehicle-administered mice. These results suggest that reduced angiogenin in response to LicA treatment may play essential role to inhibit tumor growth, angiogenesis as well as metastasis.