• Journal of Life Science
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• v.26 no.6
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• pp.673-679
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• 2016

The development of safe and effective anti-cancer compounds has been seriously required to prevent and treat development of tumor in recent years. Among them, natural compounds derived traditional medicinal stuffs have been paid to attention as an anti-cancer candidate. In this study, aesculetin is a main component of a widely known as a medicinal stuff. It was reported that aesculetin has various biological effects such as anti-inflammatory and anti-bacterial, but its effect related to cell invasion was not discovered. Therefore, in this study, the effect of aesculetin on antioxidant and matrix metalloproteases (MMPs) was investigated in human fibrosarcoma cells, HT1080. First of all, aesculetin showed the scavenging activity of DPPH radical and reducing power in a dose dependent manner. As a result of cytotoxicity, the nontoxic concentration of aesculetin was below 2 μM in HT1080 cells performed by MTT assay. In addition, aesculetin displayed the inhibitory effect on MMP-9 activity related to cell invasion in experiment carried out by gelatin zymography assay. Furthermore, aesculetin increased the expression level of TIMP-1 but decreased the expression level of MMP-9 stimulated with PMA in western blot assay. Furthermore, aesculetin remarkably inhibited cell invasion related to metastasis a dose dependent manner. Above results suggest that aesculetin could exert chemopreventive effect through inhibition of activity and expression of MMP-9 related to cell invasion.

• Journal of Life Science
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• v.26 no.8
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• pp.983-989
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• 2016

All cells composing of our body undergo their destiny such as proliferation, differentiation, necrosis, apoptosis and senescence depending on their circumstance with time. The errors occurring in these processes develop several aberrations in phenotypes including cancer, inflammation, aging and diseases. New strategy and approach are required to screen anti-aging compounds derived from natural products. Therefore, here we explain the target proteins to play a key role in aging mechanism. In the first place, matrix metalloproteinases (MMPs) are involved in metastasis, chronic inflammation and skin aging as an aging marker. In particular, histone deacetylases (HDACs) give a great attention to aging researchers who try to extend the life span of animal model. In addition, we describe the signaling pathway related to senescence which p53, IGF-1 and SIRT1 play an important role in. Furthermore, autophagy is involved in the signaling pathway associated with aging. Several new compounds modulating the signaling pathway of senescence are introduced in this review. Here, we try to provide a new insight in the molecular basis for the aging mechanism and development of aging marker. In addition, the compounds introduced here could be available for pharmaceutical applications for the prevention and the treatment of diseases related to aging.

• Journal of Life Science
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• v.20 no.5
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• pp.736-744
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• 2010

The root of Playtcodon grandiflorum, called Platycodi radix, has been a favorite edible plant in Asia and contains a large amount of saponins. Melanoma cells (B16F10) were used to investigate the inhibitory effect of aged black Platycodi radix extract (ABPRE) on oxidative stress and matrix metalloproteinases (MMPs). Platycodon radix has been known to have a variety of medicinal effects such as prevention of gastric ulcers, antiallergenic activities, histamine release inhibition, and antioxidant effects. However, the mechanism of its action remains unclear in humans. ABPRE was prepared using ethanol extraction of aged black Platycodi radix. In an antioxidant effect study of ABPRE, it was observed that ABPRE specifically exhibited the scavenging activity of DPPH radical, but did not inhibit the production of malondialdehyde from lipid peroxidation. DNA oxidation was also blocked in the presence of ABPRE. In addition, ABPRE decreased the expression and activation of MMP-2 stimulated by phenazine methosulfate. Furthermore, ABPRE revealed the inhibitory effect on melanin production induced by L-dopa via antioxidant effect and the reduction of tyrosinase expression. Especially, the expression of antioxidant enzymes such as SOD-1 and SOD-2 regulated by Nrf2 was increased in the presence of ABPRE. Therefore, it appears that ABPRE may be a possible chemopreventive agent for the prevention of metastasis related to oxidative stress.

• Journal of Life Science
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• v.24 no.6
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• pp.700-706
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• 2014

Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.

• Molecules and Cells
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• v.41 no.5
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• pp.423-435
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• 2018

This investigation was aimed at working out the combined role of lncRNA H19, miR-29b and Wnt signaling in the development of colorectal cancer (CRC). In the aggregate, 185 CRC tissues and corresponding para-carcinoma tissues were gathered. The human CRC cell lines (i.e. HT29, HCT116, SW480 and SW620) and normal colorectal mucosa cell line (NCM460) were also purchased. Si-H19, si-NC, miR-29b-3p mimics, miR-29b-3p inhibitor, si-PGRN and negative control (NC) were, respectively, transfected into the CRC cells. Luciferase reporter plasmids were prepared to evaluate the transduction activity of $Wnt/{\beta}-catenin$ signaling pathway, and dual-luciferase reporter gene assay was arranged to confirm the targeted relationship between H19 and miR-29b-3p, as well as between miR-29b-3p and PGRN. Finally, the proliferative and invasive capacities of CRC cells were appraised through transwell, MTT and scratch assays. As a result, overexpressed H19 and down-expressed miR-29b-3p displayed close associations with the CRC patients' poor prognosis (P < 0.05). Besides, transfection with si-H19, miR-29b-3p mimic or si-PGRN were correlated with elevated E-cadherin expression, decreased snail and vimentin expressions, as well as less-motivated cell proliferation and cell metastasis (P < 0.05). Moreover, H19 was verified to directly target miR-29b-3p based on the luciferase reporter gene assay (P < 0.05), and miR-29b-3p also bound to PGRN in a direct manner (P < 0.05). Finally, addition of LiCl ($Wnt/{\beta}-catenin$ pathway activator) or XAV93920 ($Wnt/{\beta}-catenin$ pathway inhibitor) would cause remarkably altered E-cadherin, c-Myc, vimentin and snail expressions, as well as significantly changed transcriptional activity of ${\beta}-catenin/Tcf$ reporter plasmid (P < 0.05). In conclusion, the lncRNA H19/miR-29b-3p/PGRN/Wnt axis counted a great deal for seeking appropriate diagnostic biomarkers and treatment targets for CRC.

• Journal of Gastric Cancer
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• v.10 no.3
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• pp.141-148
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• 2010

We have always attempted to create a standard treatment protocol for patients with gastric cancer. However, many debates still exist regarding gastric cancer treatment. For the past 2 years, at the Annual Congress of the Korean Gastric Cancer Association, we have presented a grand symposium on the "Debates on the strategy for treating gastric cancer". In 2008, four major topics were discussed and voted on after discussion. The four major topics were proximal location treatment for early gastric cancer, management choices for pyloric obstruction with advanced gastric cancer, management of liver metastasis, and reconstruction methods after a distal gastrectomy. The opinions of the audience for six minor topics were expressed by an electronic voting system. In 2009, the four main topics were treatment for submucosal tumor sized around 2 cm, laparoscopic gastrectomy in T2N1 gastric cancer, choices for managing gastric lymphoma, and application of a pylorus preserving procedure for early gastric cancer at the antrum. The opinions of the audience for these six minor topics were expressed by an electronic voting system, as was conducted in 2008. It was good opportunity to identify a point of contact about the debates on managing gastric cancer. The results of these debates and studies will identify the best methods to treat patients with gastric cancer.

• Journal of Gastric Cancer
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• v.7 no.3
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• pp.160-166
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• 2007

Purpose: Recently, chemosensitivity tests have become widely used for the selection of effective drugs in gastric cancer patients. In this study, a chemosensitivity test was performed to select agents to increase the effectiveness of adjuvant chemotherapy. Materials and Methods: Chemosensitivity testing was performed in 81 gastric cancer patients that received a gastrectomy at the Yeungnam University Hospital. An ATP (adenosine triphosphate) based chemotherapy response assay was used. Clinicopatholgical factors such as sex, age, expression of tumor markers (CEA and CA19-9 levels), location of the tumor, morphology of advanced cancer, histological type, cell differentiation, depth of invasion, Lauren classification, Ming classification, lymphatic invasion, vascular invasion, neural invasion, lymph node metastasis and TNM stage were used to correlate the chemosensitivity and clinicopathological factors. Results: The most effective antitumor agents in gastric cancer patients were (in order of effectiveness) 5-FU, Epirubicin, lrinotecan and Oxaliplatin in our series. The chemosensitivity test showed a significant difference in susceptibility according to clinicopathological factors. Conclusion: Further studies on multidrug therapy are needed to evaluate synergistic effects of drugs. Therefore, for effective chemotherapy, it is more efficacious to select a chemosensitive drug than continue to use the same drug regimen.

• Journal of Gastric Cancer
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• v.8 no.4
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• pp.198-203
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• 2008

Purpose: Multiple early gastric cancer (MEGC) accounts for between 4.5% and 11.7% of all early gastric cancers (EGC). We investigated the treatment of MEGC from the viewpoint of the clinicopathologic features of the disease. Materials and Methods: 2,281 patients with EGC underwent gastric resection at the Department of Surgery, Severance Hospital during the 11 years between January 1994 and December 2004 and we carried out a retrospective analysis of these patients. Results: There were 91 cases of synchronous MEGC (4.0%) according to the diagnostic criteria of Moertel: there were 81 double, 9 triple and 1 quadruple lesions. Of the 102 accessory lesions, 64 (62.7%) were less than 10 mm in diameter and 83 (81.4%) were located in the same region as the main lesion. The most frequent histologic type of main lesion was a well differentiated adenocarcinoma, which was found in 52 cases (57.1%). There were 49 mucosal main lesions and 42 submucosal main lesions. Lymph node metastasis was detected in 6 cases (6.6%): 1 in mucosal lesions and 5 in submucosal main lesions Conclusion: Solitary EGC and MEGC had very similar clinopathological features and a similar prognosis. Therefore, we believe that the general EGC treatment guidelines can be applied for multiple EGC. It is important to evaluate the whole stomach before and during the operation and then after examining the resected specimen.

• Journal of Chest Surgery
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• v.34 no.12
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• pp.924-929
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• 2001

Backgroun : The long-term survival after operation of patients with lung cancer invading the chest wall is known to be related to regional nodal involvement, completeness of resection and depth of chest wall involvement. In this study results of complete resection are reviewed to determine survival charateristics. Material and Method: Of 680 consecutive patients who were operated on for primary non-small cell carcinoma between 1988 and 1998, we retrospectively reviewed 55 patients(8.0%) who had complete resection for lung cancer invading the chest wall or parietal pleura. Result: Resection of the chest wall was on bloc in 29 patients(47.3％), and extrapleural in 26(52.7％). In the patients undergoing extrapleural resection, the depth of chest wall invasion was confined to the parietal pleura in all patients(100%). In the patients underging en bloc resection, the pathologic depth of invasion was into the parietal pleura alone in 9(31.0%) and into the chest wall in 20(69.0%). The follow-up rate of these patients was 100%. Hospital mortality was 5.4%(n=3). The actuarial 5-year survival rate was 26% for all hospital survivors(n=52). The actuarial 5-year survival rate of patients with T3N0M0 disease(29%) was better than that of T3N2M0 disease(18%), however, there was no significant(p=0.30) difference. The depth of chest wall invasion had no statistically significant effect on survival in our series, neither for patients with involved lymphatic metastasis nor for those without(p=0.99). Conclusion: These observations indicate that the good five year survival in patients with T3 NSCLC invading the chest wall resulted from complete resection. Survival of patients with lung cancer invading the chest wall after complete resection is dependent on the extent of nodal involvement and much less so on the depth of chest wall invasion.

• Journal of Chest Surgery
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• v.34 no.12
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• pp.930-936
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• 2001

Background: The origin site of carcinoma invading esophagogastric junction is variable. It may arise from squamous cell carcinoma of low esophagus, adenocarcinoma arising from Barrett's esophagus, adenocarcinoma of gastric cardia, or extension from proximal stomach cancer. In Korea, the majority of adenocarcinoma invading esophago-gastric junction seems to arise from proximal gastric carcinoma. Material and Method: We reviewed the data of surgically-resected gastric adenocarcinoma involving esophagogastric junction in KCCH between 1988 and 1999. Result: There were 212 cases. Male to female ratio was 156 to 56. Age distribution was between 22 and 78. Variable surgical approaches including median laparotomy, laparotomy with left or right thoracotomy, left thoracotomy, and thoracoabdominal approach were used. Postoperative pathologic stages were : Stage IA-7, IB-11, Ⅱ-25, ⅢA-73, ⅢB-34, and Ⅳ-57. Curative resection was performed in 199 patients, and total gastrectomy was performed in 200 patients. There were 77.4%(164 cases) with esophageal involvement, 74.1％(157 cases) with tumor involvement in the abdominal LN, and 8%(17 cases) with mediastinal LN metastasis. Operative mortality was 3.3%, and over-all 5 year survival rate was 35%. Conclusion: There are various surgical approaches and many things to consider for surgical resection, thoracic and abdominal approach may need for obtain proper resection margin and adequate lymph node dissection in stomach cancer invading esophagogastric junction.