• IMMUNE NETWORK
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• v.12 no.2
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• pp.66-69
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• 2012

The immunological death induction by EY-6 on the human tumor cell lines was screened. Human colon carcinoma (HCT15, HCT116), gastric carcinoma (MKN74, SNU668), and myeloma (KMS20, KMS26, KMS34) cells were died by EY-6 treatment with dose-dependent manner. CRT expression, a typical marker for the immunological death, was increased on the EY-6-treated colorectal and gastric cancer cells. Interestingly, the effects on the myeloma cell lines were complicated showing cell line dependent differential modulation. Cytokine secretion from the EY-6 treated tumor cells were dose and cell-dependent. IFN-${\gamma}$ and IL-12 secretion was increased in the treated cells (200% to over 1000% of non-treated control), except HCT116, SNU668 and KMS26 cells which their secretion was declined by EY-6. Data suggest the potential of EY-6 as a new type of immuno-chemotherapeutics inducing tumor-specific cell death. Further studies are planned to confirm the efficacy of EY-6 including in vivo study.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.7
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• pp.3045-3050
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• 2014

Renal cell carcinoma (RCC) is the most lethal of all urological cancers and tumor angiogenesis is closely related with its growth, invasion, and metastasis. Recent studies have suggested that epidermal growth factor-like domain multiple 7 (EGFL7) is overexpressed by many tumors, such as colorectal cancer and hepatocellular carcinoma; it is also correlated with progression, metastasis, and a poor prognosis. However, the role of EGFL7 in RCC is not clear. In this study, we examined how EGFL7 contributes to the growth of RCC using a co-culture system in vitro and a xenograft model in vivo. Downregulated EGFL7 expression in RCC cells affected the migration and tubule formation of HMEC-1 cells, but not their growth and apoptosis in vitro. The level of focal adhesion kinase (FAK) phosphorylation in HMEC-1 cells decreased significantly when co-cultured with 786-0/iEGFL7 cells compared with 786-0 cells. After adding rhEGFL7, the level of FAK phosphorylation in HMEC-1 cells was significantly elevated compared with phosphate-buffered saline (PBS) control. However, FAK phosphorylation was abrogated by EGFR inhibition. The average size of RCC local tumors in the 786-0/iEGFL7 group was noticeably smaller than those in the 786-0 cell group and their vascular density was also significantly decreased. These data suggest that EGFL7 has an important function in the growth of RCC by facilitating angiogenesis.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.17
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• pp.6989-6999
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• 2014

Colorectal cancer (CRC) is one of the major healthcare problems worldwide and its processes of genesis include a sequence of molecular pathways from adenoma to carcinoma. The discovery of microRNAs, a subset of regulatory non-coding RNAs, has added new insights into CRC diagnosis and management. Together with several causes of colorectal neoplasia, aberrant expression of oncomiRs (oncogenic and tumor suppressor miRNAs) in cancer cells was found to be indirectly result in up- or down-regulation of targeted mRNAs specific to tumor promoter or inhibitor genes. The study of miRNAs as CRC biomarkers utilizes expression profiling methods from traditional tissue samples along with newly introduced non-invasive samples of faeces and body fluids. In addition, miRNAs could be employed to predict chemo- and radio-therapy responses and be manipulated in order to alleviate CRC characteristics. The scope of this article is to provide a comprehensive review of scientific literature describing aberrantly expressed miRNAs, and consequently dysregulation of targeted mRNAs along with the potential role of miRNAs in CRC diagnosis and prognosis, as well as to summarize the recent findings on miRNA-based manipulation methods with the aim of advancing in anti-CRC therapies.

• Journal of Life Science
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• v.31 no.4
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• pp.400-409
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• 2021

Sanguinarine, a natural benzophenanthridine alkaloid, has been considered a potential therapeutic target for the treatment of cancer because it can induce apoptosis in human cancer cells; however, the underlying mechanisms of action still remain unclear. Tumor suppressor p53 deletion or mutation is an important reason for the resistance of colorectal cancer cells to anticancer agents. Therefore, in the present study, the role of p53 during apoptosis induced by sanguinarine was investigated in p53wild type (WT, p53+/+) and p53null (p53+/+) HCT116 colon carcinoma cells. Sanguinarine significantly caused greater reductions in cell viability in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells. Consistently, sanguinarine promoted more DNA damage and apoptosis in HCT116 (p53+/+) cells than in HCT116 (p53-/-) cells while increasing the expression of p53 and cyclin-dependent kinase inhibitor p21^WAF1/CIP1. Sanguinarine increased the activity of caspase-8 and caspase-9, which are involved in the initiation of extrinsic and intrinsic apoptosis pathways, respectively, and it activated caspase-3, a typical effect caspase, in HCT116 (p53+/+) cells. Sanguinarine also increased the generation of reactive oxygen species (ROS), and the Bax/Bcl-2 ratio, while destroying the integrity of mitochondria in HCT116 (p53+/+) cells, but not in HCT116 (p53-/-) cells. Overall, the results indicate that sanguinarine induced p53-dependent apoptosis through ROS-mediated activation of extrinsic and intrinsic apoptotic pathways in HCT116 colorectal cancer cells.

• International Journal of Oral Biology
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• v.47 no.1
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• pp.9-15
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• 2022

Humulus japonicus (HJ) is a widely used herbal medicine for pulmonary tuberculosis, hypertension, leprosy, and venomous wounds in Asia, particularly in China. Although HJ has certain physiological activities, such as longitudinal bone growth, antioxidation and alleviation of rheumatism, its anticancer activities, other than in colorectal and ovarian cancer, are yet to be studied. In this study, we investigated the anti-cancer activity and mechanism of methanol extracts of HJ (MeHJ) against human FaDu hypopharyngeal squamous carcinoma cells. MeHJ suppressed FaDu cell viability without affecting normal cells (L929), which was demonstrated using the MTT and Live & Dead assays. Furthermore, MeHJ effectively inhibited colony formation of FaDu cells, even at non-cytotoxic concentrations, and significantly induced apoptosis through the proteolytic cleavage of caspase-9, -3, -7, poly (ADP-ribose) polymerase and through the downregulation of BCL-2 and upregulation of BAX in FaDu cells, as determined by DAPI staining, flow cytometry, and western blot analyses. Collectively, these findings suggest that the inhibitory effects of MeHJ on the growth and colony formation of oral cancer cells may be mediated by caspase- and mitochondrial-dependent apoptotic pathways in human FaDu hypopharyngeal squamous carcinoma cells. Therefore, MeHJ has the potential to be used as a natural chemotherapeutic drug against human oral cancer.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2023.04a
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• pp.50-50
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• 2023

Prostaglandin E2(PGE2), a major product of cyclooxygenase-2 (COX-2), plays an important role in the carcinogenesis of many solid tumors, including colorectal cancer. Because PGE2 functions by signaling through PGE2 receptors (Eps), which regulate tumor cell growth, invasion, and migration, there has been a growing amount of interest in the therapeutic potential of targeting Eps. In the present study, we investigated the role of EP4 on the effectiveness of cordycepin in inhibititing the migration and invasion of HCT116 human colorectal carcinoma cells. Our data indicate that cordycepin suppressed lipopolysaccharide (LPS)-enhanced cell migration and invasion through the inactivation of matrix metalloproteinases (MMP)-9 as well as the down-regulation of COX-2 expression and PGE2 production. These events were shown to be associated with the inactivation of EP4 and activation of AMP-activated protein kinase (AMPK). Moreover, the AMPK inhibitor, compound C, as well as AMPK knockdown via siRNA, attenuated the cordycepin-induced inhibition of EP4 expression. Cordycepin treatment also reduced the activation of CREB. These findings indicate that cordycepin suppresses the migration and invasion of HCT116 cells. Through modulating EP4 expression and the AMPK-CREB signaling pathway. Therefore, cordycepin has the potential to serve as a potent anti-cancer agent in therapeutic strategies against colorectal cancer metastasis.

• The Korean Journal of Cytopathology
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• v.8 no.2
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• pp.115-119
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• 1997

Cytologic diagnosis of reactive or malignant effusion is sometimes difficult. Especially, differentiation of benign reactive mesothelial cells from malignant cells in body effusion is more difficult. Recently, immunohistochemistry has been used to diagnose difficult cases. Phospholipase $C(PLC)-{\gamma}1$ is one of the isoenzyme of the PLC which plays central role in signal transduction involving cellular growth, differentiation and transformation by phosphorylating many protein component. Increased expression of $PLC-{\gamma}1$ in human breast carcinoma, colorectal carcinoma and stomach cancers are reported. To evaluate the efficacy of positive $PLC-{\gamma}1$ immunostaining in the diagnosis of malignancy in effusions, paraffin-embedded cell blocks of pleural fluid and ascites from 10 patients(5 metastatic adenocarcinomas, and 5 reactive mesothelial cells) were immunostained with a monoclonal antibody to $PLC-{\gamma}1$. $PLC-{\gamma}1$ immuostained all the adenocarcinomas in cell block(5/5) with intense membrane pattern, however, none of the reactive mesothelial proliferations stained with the diagnostic membrane pattern. Thus, our study strongly supports the conclusion that $PLC-{\gamma}1$ immunopositivity is likely to become a useful adjunct for the diagnosis of malignancy in effusions.

• Food Science and Biotechnology
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• v.17 no.6
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• pp.1265-1271
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• 2008

Adlay bran is a waste product previously thought to have no commercial value, Its methanolic extract was fractionated using n-hexane (ABM-Hex), ethyl acetate (ABM-EtOAc), 1-butanol (ABM-BuOH), and water (ABM-$H_2O$). The ABM-EtOAc fraction exhibited a strongest inhibition against growth of human lung cancer cell A549 and human colorectal carcinoma cells HT-29 and COLO 205. Inhibition of cell cycle progression at $G_0/G_1$ transition, increase of cells at the sub-$G_1$ phase, and DNA ladders were observed in cells treated with ABM-EtOAc. The ABM-BuOH fraction showed the strongest inhibition of proinflammatory cytokines tumor necrosis factor (TNF)-$\alpha$ and interlukin (IL)-$1{\beta}$ in stimulated RAW 264.7 macrophages. Further, ABM-EtOAc and ABM-BuOH inhibited cyclooxygenase (COX)-2 expression in A549 and HT-29 carcinoma cells, while COX-l expression was not affected. These results reveal that both ABM-EtOAc and ABM-BuOH may aid the prevention of cancers and the applications in cancer chemotherapy.

• Proceedings of the Korean Society of Life Science Conference
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• 2003.05a
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• pp.147-147
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• 2003

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.253-256
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• 2014

Background: The standard treatment in the metastatic colorectal cancer consists of 5-FU based infusional regimens. However, with oral fluoropyrimidines, equal tumor responses may be obtained. Capecitabine causes macrocytosis of the cells by inhibition of DNA synthesis. In this context, a relationship was found between mean corpuscular volume (MCV) and response to therapy in breast cancer patients treated with Capecitabine, but whether this relationship also pertains in colorectal cancer has not been established. Materials and Methods: A total of 102 metastatic colorectal cancer patients treated with a oxaliplatin (XELOX)${\pm}$Bevacizumab combination were retrospectively evaluated. Patients were randomized into three groups. Hematological parameters (MCV, MPV, PCT, PLT, NLR) were recorded retrospectively, before treatment and after 3 cycles of chemotherapy. Results: After three cycles of therapy, 20 (19.6%) patients had progressive disease (PD), 41 (40.1%) had stable disease (SD), and 41 (40.1%) demonstrated a partial response (PR). In 62 (60.7%) treatment was with capesitabin plus XELOX therapy, and in 40 (39.2%) it was XELOX-Bevacizumab combination therapy. There was no difference among three groups before the treatment in terms of MCV, MPV, PCT, PLT, and NLR. MCV showed significant increase in chemotherapy response groups (PR and SD). In addition, a significant decrease was observed for platelet count in chemotherapy response groups. While NLR decrease was seen in only a PR group, PCT decrease was observed in all three groups. PCT and PLT values were higher in patients receiving Bevacizumab. Conclusions: PLT, PCT, MPV, and NLR values were decreased due to Capecitabine-based chemotherapy, however MCV was increased. PCT and PLT values were higher in patients who received Bevacizumab than those who did not. MCV, PLT, and NLR can be considered as important factors in predicting response to colorectal carcinoma treatment.