• Title/Summary/Keyword: cancer invasiveness

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A Fermented Ginseng Extract, BST204, Inhibits Proliferation and Motility of Human Colon Cancer Cells

  • Park, Jong-Woo;Lee, Jae-Cheol;Ann, So-Ra;Seo, Dong-Wan;Choi, Wahn-Soo;Yoo, Young-Hyo;Park, Sun-Kyu;Choi, Jung-Young;Um, Sung-Hee;Ahn, Seong-Hoon;Han, Jeung-Whan
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.211-217
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    • 2011
  • Panax ginseng CA Meyer, a herb from the Araliaceae, has traditionally been used as a medicinal plant in Asian countries. Ginseng extract fermented by ginsenoside-${\beta}$-glucosidase treatment is enriched in ginsenosides such as Rh2 and Rg3. Here we show that a fermented ginseng extract, BST204, has anti-proliferative and anti-invasive effects on HT-29 human colon cancer cells. Treatment of HT-29 cells with BST204 induced cell cycle arrest at $G_1$ phase without progression to apoptosis. This cell cycle arrest was accompanied by up-regulation of tumor suppressor proteins, p53 and p21$^{WAF1/Cip1}$, down-regulation of the cyclin-dependent kinase/cyclins, Cdk2, cyclin E, and cyclin D1 involved in $G_1$ or $G_1/S$ transition, and decrease in the phosphorylated form of retinoblastoma protein. In addition, BST204 suppressed the migration of HT-29 cells induced by 12-O-tetradecanoylphorbol-13-acetate, which correlated with the inhibition of metalloproteinase-9 activity and extracellular signal-regulated kinase activity. The effects of BST204 on the proliferation and the invasiveness of HT-29 cells were similar to those of Rh2. Taken together, the results suggest that fermentation of ginseng extract with ginsenoside-${\beta}$-glucosidase enhanced the anti-proliferative and the anti-invasive activity against human colon cancer cells and these anti-tumor effects of BST204 might be mediated in part by enriched Rh2.

AZD1480 Can Inhibit the Biological Behavior of Ovarian Cancer SKOV3 Cells in vitro

  • Sun, Zhao-Ling;Tang, Ya-Juan;Wu, Wei-Guang;Xing, Jun;He, Yan-Fang;Xin, De-Mei;Yu, Yan-Li;Yang, Yang;Han, Ping
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4823-4827
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    • 2013
  • Objective: To study the mechanism of effects of AZD1480 on the SKOV3 ovarian cancer cell line. Methods: The MTT method was used to assess cellular proliferation, flow cytometry for cellular apoptosis, the scratch test to determine migration, transwell chamber assays to detect cellular invasion, plate clone experiments to detect the clone forming ability and Western blotting to determine p-STAT3 protein levels. Results: The proliferation rate, migration ability, invasiveness and the clone forming ability of SKOV3 cells were reduced after treatment with AZD1480, while apoptosis rate and chemotherapeutic susceptibility were increased. After treatment with AZD1480 plus cisplatin, the apoptosis rate increased significantly while the expression level of p-STAT3 protein was decreased. Conclusion: AZD1480 can inhibit the proliferation, invasion, metastasis and clone formation of SKOV3 cells, induce cellulsar apoptosis, increase the chemotherapeutic sensitivity and reduce the expression level of p-STAT3 protein.

Intracorporeal Anastomosis Using Linear Stapler in Laparoscopic Distal Gastrectomy: Comparison between Gastroduodenostomy and Gastrojejunostomy

  • Lee, Hak-Woo;Kim, Hyoung-Il;An, Ji-Yeong;Cheong, Jae-Ho;Lee, Kang-Young;Hyung, Woo-Jin;Noh, Sung-Hoon
    • Journal of Gastric Cancer
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    • v.11 no.4
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    • pp.212-218
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    • 2011
  • Purpose: Intracorporeal anastomosis during laparoscopic gastrectomy is becoming increasingly prevalent. However, selection of the anastomosis method after laparoscopic distal gastrectomy is equivocal because of a lack of technical feasibility and safety. We compared intracorporeal gastroduodenostomy with gastrojejunostomy using linear staplers to evaluate the technical feasibility and safety of intracorporeal anastomoses as well as its' minimally invasiveness. Materials and Methods: Retrospective analyses of a prospectively collected database for gastric cancer revealed 47 gastric cancer patients who underwent laparoscopic distal gastrectomy with either intracorporeal gastroduodenostomy or gastrojejunostomy from March 2011 to June 2011. Perioperative outcomes such as operation time, postoperative complication, and hospital stay were compared according to the type of anastomosis. Postoperative inflammatory response was also compared between the two groups using white blood cell count and high sensitivity C-reactive protein. Results: Among the 47 patients, 26 patients received gastroduodenostomy, whereas 21 patients received gastrojejunostomy without open conversion or additional mini-laparotomy incision. There was no difference in mean operation time, blood loss, and length of postoperative hospital stays. There was no statistically significant difference in postoperative complication or mortality between two groups. However, significantly more staplers were used for gastroduodenostomy than for gastrojejunostomy (n=6) than for gastroduodenostomy and (n=5). Conclusions: Intracorporeal anastomosis during laparoscopic gastrectomy using linear stapler, either gastroduodenostomy or gastrojejunostomy, shows comparable and acceptable early postoperative outcomes and are safe and feasible. Therefore, surgeons may choose either anastomosis method as long as oncological safety is guaranteed.

TIMP-2 Gene Transfer Via Adenovirus Inhibits the Invasion of Lung Cancer Cell (TIMP-2 유전자 재조합 아데노바이러스의 폐암세포 침윤 억제 효과)

  • Oh, Yeon-Mok;Lee, Jae-Ho;Yoo, Chul-Gyu;Chung, Hee-Soon;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Lee, Choon-Taek
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.2
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    • pp.189-197
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    • 2000
  • Background : Tissue inhibitor of metalloproteinase is a natural inhibitor that counteracts pro teolytic enzymes essential to the invasion of cancer cell. Whether or not TIMP-2 gene transfer via adenovirus could inhibit the invasion of lung cancer cell iη vitro was evaluated for the future purpose of gene therapy against lung cancer. Methods : Recombinant adenovirus-TIMP-2(Ad-TIMP-2) was generated by homologous recombination after pACCMV-TIMP-2 and pJM17 were cotransfected into 293 cell by standard calcium phosphate coprecipitate method. Calu-6, one of the most invasive lung cancer cells, was transduced with Ad-TIMP-2 or Ad-$\beta$gal. Anchorage-independent growth and invasiveness were assessed by soft agar clonogenicity assay and invasion assay using two-chamber, well divided by matrigel. Results : Ad-TIMP-2 transduced calu-6 cells produced biologically active TIMP-2 more than 50 times more than parental calu-6. TIMP-2 gene transfer did not suppress the in vitro tumorigenicity. However, two chamber well assay revealed that Ad-TIMP-2 transduction reduced the invasiveness of calu-6 efficiently (12% compared with parental cell) even at low 10moi. Conclusion : Even though TIMP-2 gene transfer did not inhibit in vitro tumorigenicity, it did inhibit invasion of lung cancer cell in vitro. The inhibition of invasion by Ad-TIMP-2 may be a useful strategy for the treatment of lung cancer.

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At Which Stage of Gastric Cancer Progression Do Levels of Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 Increase? Application in Advanced Gastric Cancer Treatment

  • Han, Eui Soo;Lee, Han Hong;Lee, Jun Suh;Song, Kyo Young;Park, Cho Hyun;Jeon, Hae Myung
    • Journal of Gastric Cancer
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    • v.14 no.2
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    • pp.123-128
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    • 2014
  • Purpose: Since there are no proven tumor markers that reflect the course of gastric cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) are commonly used alternatives. However, the degree of progression that corresponds to an increase in these markers, and the values of these markers at different cancer stages, remains unclear. Materials and Methods: This study enrolled 1,733 gastric cancer patients who underwent surgery and whose pre-operative CEA and CA19-9 levels were known. Survival curves and mean values of the two markers were compared according to the degree of cancer progression: serosa-unexposed (SU), serosa-exposed (SE), direct invasion (DI), localized seeding (P1), and extensive seeding (P2). Results: The 5-year overall survival rates at each stage differed significantly, except between DI and P1 patients (17.1% vs. 10.5%, P=0.344). The mean CEA values in SU, SE, DI, P1, and P2 patients were 5.80, 5.48, 13.36, 8.06, and 22.82, respectively. The CA19-9 values for these patients were 49.40, 38.97, 101.67, 73.77, and 98.57, respectively. The increase in CEA in P2 patients was statistically significant (P=0.002), and the increases in CA19-9 in DI and P2 patients were significant (P=0.025, 0.007, respectively). There was a fair correlation between the two markers in P2 patients (r=0.494, P<0.001). Conclusions: CA19-9 can be used to assess DI of gastric cancer into adjacent organs. Both markers are useful for predicting the presence of extensive peritoneal seeding.

Knockdown of Ezrin by RNA Interference Reverses Malignant Behavior of Human Pancreatic Cancer Cells in Vitro

  • Zhong, Zhi-Qiang;Song, Mao-Min;He, Ying;Cheng, Shi;Yuan, Hui-Sheng
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.8
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    • pp.3781-3789
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    • 2012
  • Background: Pancreatic cancer is one of the most aggressive tumors with a dismal prognosis. The membrane cytoskeletal crosslinker Ezrin participates in several functions including cell proliferation, adhesion, motility and survival. There is increasing evidence that Ezrin is overexpressed in vast majority of malignant tumors and regulates tumor progression. However, its roles in pancreatic cancer remain elusive. Methods: Three pairs of specific Ezrin siRNAs were designed and synthetized and screened to determine the most efficient one for construction of a hairpin RNA plasmid targeting Ezrin. After transfection into the Panc-1 pancreatic cancer cell line, real-time quantitative PCR and Western blotting were performed to examine the expression of mRNA and protein. The MTT method was applied to examine the proliferation and the drug sensibility to Gemcitabine. Flow cytometry was used to assess the cycle and apoptosis, while capacity for invasion was determined with transwell chambers. Furthermore, we detected phosphorylated-Erk1/2 protein and phosphorylated-Akt protein by Western blotting. Results: Real-time quantitative PCR and Western blotting revealed that Ezrin expression was notably down-regulated at both mRNA and protein levels by RNA interference (P< 0.01). Proliferation was inhibited and drug resistance to gemcitabine was improved (P< 0.05). Flow cytometry showed that the proportion of cells in the G1/G0 phase increased (P< 0.01), and in G2/M and S phases decreased (P< 0.05), with no apparent differences in apoptosis (P> 0.05). The capacity for invasion was markedly reduced (P< 0.01). In addition, down-regulating Ezrin expression had no effect on phosphorylated-Akt protein (P>0.05), but could decrease the level of phosphorylated-Erk1/2 protein (P< 0.05). Conclusions: RNA interference of Ezrin could inhibit its expression in the pancreatic cancer cells line Panc-1, leading to a potent suppression of malignant behavior in vitro. Assessment of potential as a target for pancreatic cancer treatment is clearly warranted.

Polarization of M2 Macrophages by Interaction between Prostate Cancer Cells Treated with Trichomonas vaginalis and Adipocytes

  • Chung, Hyo-Yeoung;Kim, Jung-Hyun;Han, Ik-Hwan;Ryu, Jae-Sook
    • 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.

Normal Human Pleural Surface Area Calculated by Computed Tomography Image Data

  • Kim, Doo-Sang;Roh, Hyung-Woon
    • International Journal of Vascular Biomedical Engineering
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    • v.4 no.1
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    • pp.27-30
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    • 2006
  • Background; Pleural micro-metastasis of lung cancer is detected by touch print cytology or pleural lavage cytology, but its prognostic impact has not elucidated yet. We hypothesize that recurrence may depend on the amount of tumor cells disseminated in pleural cavity, if the invasiveness of all cancer is the same. To predict the amount of tumor cells disseminated in pleural cavity, we need pleural surface area, distributed pattern of cells and concentration of cells per unit area. Human pleural surface area has not reported yet. In this report, we calculate the normal human pleural surface area using CT image data processing. Methods; Twenty persons were checked CT scan, and we obtained the data from each image. In order to calculate the pleural surface, the outline of lung was firstly extruded from CT image data using home-made Digitizer program. And the distance between CT images was calculated from the extruded outline. Finally a normal human pleural surface was calculated from function between the distance of consecutive CT images and the calculated length. Results; Their mean age is $65{\pm}12$ years old (range $26{\sim}77$), body weight is $62{\pm}9\;kg\;(48{\sim}80)$, and height is $167{\pm}6\;cm\;(156{\sim}176)$. The number of images used is $36{\pm}7\;(24{\sim}51)$. Pleural surface area is $211,888{\pm}35,756\;mm^2\;(143,880{\sim}279,576)$. Right-side pleural surface area is $107,932\;mm^2$ and Lt is $103,955\;mm^2$. Costal, mediastinal and diaphragmatic surfaces of right-side pleura are $77,483\;mm^2,\;39,057\;mm^2,\;and\;8,608\;mm^2$ respectively, and left-side are $72,497\;mm^2,\;35,578\;mm^2,\;and\;4,120\;mm^2$ respectively. Conclusion; Normal human pleural surface area is calculated using CT image data at first and the result is about $0.212\;m^2$.

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Serum Level of Matrix Metalloproteinase-2 and -9 in Patients with Laryngeal Squamous Cell Carcinoma and Clinical Significance

  • Lotfi, Alireza;Mohammadi, Ghodrat;Saniee, Lale;Mousaviagdas, Mehrnoosh;Chavoshi, Hadi;Tavassoli, Atena
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6749-6751
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    • 2015
  • Background: Laryngeal cancer is an important malignancy in head and neck area and squamous cell carcinoma (SCC) is the most common type accounting for 95% of cases. Increase in matrix metalloproteinases (MMPs) in different tumors and their correlation with tumor invasiveness has been documented. However, most studies have evaluated MMP-2 and MMP-9 expression and few have evaluated serum levels. The aim of current study was to evaluate serum levels in patients with laryngeal SCC compared to normal subjects and assess any relation with tumor clinicopathological findings. Materials and Methods: In this case control study, 20 patients with oral SCC and 20 healthy subjects were included. Serum levels of MMP-2 and MMP-9 were compared between groups and correlations with findings including grade (T) and node involvement (N) were evaluated. Results: Patients with laryngeal SCC had significantly higher serum levels of MMP-2 (p=0.01) and MMP-9 (p=0.03) compared to healthy subjects. Patients with higher T stage (T3,4) had significantly higher MMP-2 (p=0.04) and MMP-9 (p=0.01). There was significant positive correlation between serum levels of MMP-2 with T stage (r=0.45, p=0.04) and lymph node involvement (r=0.563, p=0.01) and between levels of MMP-9 with T stage (r=0.527, p=0.01). Conclusions: Our results showed that compared to healthy subjects, both MMP-2 and MMP-9 are significantly increased in serum of laryngeal SCC cases. MMP-2 was correlated with lymph node involvement while MMP-9 has stronger correlation with T stage compared to MMP-2.

Glutathione S-Transferase Expression in Upper Urinary Tract Urothelial Carcinomas: a Taiwan Study

  • Chen, Szu-Han;Wu, Wen-Jeng;Tu, Hung-Pin;Li, Wei-Ming;Huang, Chun-Nung;Li, Ching-Chia;Lin, Hui-Hui;Ke, Hung-Lung
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6475-6479
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    • 2013
  • Objectives: Glutathione S-transferase (GST) isoenzymes play important roles in resistance to cell apoptosis and carcinogenesis. We aimed to establish the relationship between GST expression and the prognosis of upper urinary tract urothelial carcinoma (UTT-UC) in Taiwan. Methods: This study retrospectively reviewed 46 patients with pathologically confirmed UUT-UC at Kaohsiung Medical University Hospital. In each patient, expression of GSTT1 and GSTP1 was compared between urothelial carcinoma and normal urothelial cells by Western blotting. Results: GSTP1 expression in the UUT-UC cells was significantly higher than that in normal urothelial cells (1.6 fold, p<0.001). Expression of GSTT1 was significantly associated with the invasiveness of the carcinoma (p=0.006). Conclusions: In UUT-UC, GSTP1 might be a potential tumor marker, whereas high GSTT1 expression could be used as an indicator of cancer progression. This study is the first to demonstrate potential applications of different GST isoenzymes for biomolecular analysis of UUT-UCs in Taiwan.