• YAKHAK HOEJI
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• v.40 no.6
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• pp.690-696
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• 1996

It has been known that many kinds of cancer are caused by continued proliferation or abnormal differentiation. Thus, recent approaches to anticancer therapy have been focused on developing drugs that induce differentiation of cancer cells to normal cells. A typical differentiation agent, all trans-retinoic acid, is unsuitable for anticancer drug because all trans-retinoic acid produces unfavorable side effects and cytotoxicity in normal cells. Therefore, we have screened some new differentiation-inducing compounds obtained from marine organisms using F9 teratocarcinoma stem cells as a model system. We observed that fatty acid. glycolipid, saponin, sphingosine and sterol compounds of marine organisms had differentiation-inducing activity in F9 cells, were determined by morphological changes and Northern blot analysis. The expression of differentiation marker genes, such as laminin B1, type IV collagen and retinoic acid receptor beta were induced by treatment with those compounds.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2145-2148
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• 2012

Objective: This study concerns expression of PBK/TOPK during differentiation of HL-60 leukemic cells induced by tetradecanoyl phorbol acetate (TPA). Methods: Wright-Giemsa staining was performed to observe morphological changes in the HL-60 cells, and flow cytometry was used to assess the cell cycle and CD11b, CD14, CD13, and CD33 expression. PBK/TOPK levels were determined by Western blot analysis. Results: After treating HL60 cells with $5.1{\times}10^{-9}$ mmol/L of TPA for three days, the number of nitroblue-tetrazolium-positive cells and CD11b, CD13, and CD14 expression increased, whereas the PBK/TOPK levels decreased. Conclusions: TPA can inhibit proliferation and induce differentiation of HL60 cells of the granulocytic or monocytic lineage. PBK/TOPK expression was downregulated during this process, whereas the Pho-PBK/TOPK expression was increased.

• BMB Reports
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• v.36 no.1
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• pp.110-119
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• 2003

The acetylation state of histone is reversibly regulated by histone acetyltransferase (HAT) and deacetylase (HDAC). An imbalance of this reaction leads to an aberrant behavior of the cells in morphology, cell cycle, differentiation, and carcinogenesis. Recently, these key enzymes in the gene expression were cloned. They revealed a broad use of this modification, not only in histone, but also other proteins that involved transcription, nuclear transport, and cytoskeleton. These results suggest that HAT/HDAC takes charge of multiple-functions in the cell, not just the gene expression. HDAC is especially known to play an important role in carcinogenesis. The enzyme has been considered a target molecule for cancer therapy. The inhibition of HDAC activity by a specific inhibitor induces growth arrest, differentiation, and apoptosis of transformed or several cancer cells. Some of these inhibitors are in a clinical trial at phase I or phase II. The discovery and development of specific HDAC inhibitors are helpful for cancer therapy, and decipher the molecular mode of action for HDAC.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.16 no.4
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• pp.508-514
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• 1994

For the complete cure of oral cancer suspected to have invaded the mandible in clinical & radiological evaluation, the mandible resection in planned. The aim of this clinical study was to help in decision making in the method & the extent of the mandibular resection surgery. This study was conducted on 46 oral cancer patients, who received cancer surgery including mandibulectomy. And we evaluated the relationship between the pathologic results of resected mandible and the location, size and clinical newk node involvement, tumor cell differentiation. The results are that ; (1) Hiher incidence of bone invasion patterns were observed in tumor of mouth floor & gingiva compared to those of tongue & tonsil, and (2) No significant relationship was found between bone invasion of tumor and tumor size, neck node involvement tumor cell differentiation. The approximation between tumor and bone seems to be the most reliable factor among the other factors in decision making of mandibular resection.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.6813-6823
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• 2015

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most aggressive of human brain tumors and has a stunning progression with a mean survival of one year from the date of diagnosis. High cell proliferation, angiogenesis and/or necrosis are histopathological features of this cancer, which has no efficient curative therapy. This aggressiveness is associated with particular heterogeneity of the tumor featuring multiple genetic and epigenetic alterations, but also with implications of aberrant signaling driven by growth factors. The transforming growth factor ${\beta}$ ($TGF{\beta}$) superfamily is a large group of structurally related proteins including $TGF{\beta}$ subfamily members Nodal, Activin, Lefty, bone morphogenetic proteins (BMPs) and growth and differentiation factor (GDF). It is involved in important biological functions including morphogenesis, embryonic development, adult stem cell differentiation, immune regulation, wound healing and inflammation. This superfamily is also considered to impact on cancer biology including that of GBM, with various effects depending on the member. The $TGF{\beta}$ subfamily, in particular, is overexpressed in some GBM types which exhibit aggressive phenotypes. This subfamily impairs anti-cancer immune responses in several ways, including immune cells inhibition and major histocompatibility (MHC) class I and II abolishment. It promotes GBM angiogenesis by inducing angiogenic factors such as vascular endothelial growth factor (VEGF), plasminogen activator inhibitor (PAI-I) and insulinlike growth factor-binding protein 7 (IGFBP7), contributes to GBM progression by inducing metalloproteinases (MMPs), "pro-neoplastic" integrins (${\alpha}v{\beta}3$, ${\alpha}5{\beta}1$) and GBM initiating cells (GICs) as well as inducing a GBM mesenchymal phenotype. Equally, Nodal promotes GICs, induces cancer metabolic switch and supports GBM cell proliferation, but is negatively regulated by Lefty. Activin promotes GBM cell proliferation while GDF yields immune-escape function. On the other hand, BMPs target GICS and induce differentiation and sensitivity to chemotherapy. This multifaceted involvement of this superfamily in GBM necessitates different strategies in anti-cancer therapy. While suppressing the $TGF{\beta}$ subfamily yields advantageous results, enhancing BMPs production is also beneficial.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2525-2528
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• 2013

The Homer protein family, also known as the family of cytoplasmic scaffolding proteins, which include three subtypes (Homer1, Homer2, Homer3). Homer3 can regulate transcription and play a very important role in the differentiation and development for some tissues (e.g. muscle and nervous systems). The current studies showed that Homer3 abnormal expression changes in acute myeloid leukemia (AML). Forced expression of Homer3 in transfected K562 cells inhibited proliferation, influenced the cell cycle profile, affected apoptosis induced by $As_2O_3$ through inhibition of Bcl2 expression, and also promoted cell differentiation induced by 12-O-tetra decanoylphorbol-acetate (TPA). These results showed that Homer3 is a novel gene which plays a certain role in the occurrence and development of AML.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.3
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• pp.2005-2008
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• 2013

Background: Pemetrexed (PEM) is effective in first-line treatment for patients with non-squamous non-small cell lung cancer (NSCLC). However there are currently no definitive determinants to certify which patients could benefit from PEM. To improve the efficacy of PEM combined with platinum as first-line therapy for advanced non-squamous NSCLC, we conducted this retrospective study to detect potential determinants of this regimen. Methods: We recruited 109 patients with advanced non-squamous NSCLC who received PEM with a platinum as first-line therapy from June 2006 to February 2013 in Jiangsu Cancer Hospital. Multiple variables (age, sex, smoking, degree of cell differentiation, hemoglobin, platinum drugs combined, positions of metastasis) were selected. Logistic regression analysis was used to analyse relationships between these variables and tumor response. Result: In univariate analysis, we found that age and platinum significantly influenced the results of PEM therapy (P<0.05). In multivariable analysis, no factors were independently significant. Conclusion: Our analysis did not suggest that the age, sex, metastasis of liver or other organs, hemoglobin, smoking history and pathological differentiation are associated with the response of PEM. We should conduct further analyses with larger sample size to reconfirm this issue.

• Tuberculosis and Respiratory Diseases
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• v.68 no.1
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• pp.10-15
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• 2010

Background: Lung cancer is the most common cause of cancer mortality in Korea. The TNM stage at presentation in patients with non-small cell lung cancer (NSCLC) has the greatest impact on prognosis. Patients who undergo a complete resection for NSCLC are likely to develop recurrent and/or metastatic disease. There are several factors influencing the development of recurrence. We explored risk factors of recurrence in patients with stages I and II NSCLC, who had undergone curative resection. Methods: We reviewed patients who had complete surgical resection as definitive treatment for stage I or II. Patients followed up for more than 36 months. We evaluated several factors which might have relationship with recurrence, such as patient's demographic factors, TNM staging, pathologic finding, tumor markers and surgical technique. Results: A total of 75 patients were enrolled for analysis, of whom 58 were men and 17 were women with mean age of 61 (range, 37 to 76) years. The average size of tumors was 3.9 cm (0.7 to 10 cm). There were 64 patients with stage I NSCLC and 11 with stage II NSCLC. Among 64 patients with stage I NSCLC, 35 patients showed recurrences whereas 8 patients have recurred in stage II NSCLC. Grade of differentiation of tumor was closely related to the recurrence. Seventy-five percent of patients who had poor tumor differentiation experienced a recurrence. In contrast, 3 patients of twelve had recurrences, who revealed differentiation in their tissue (p<0.05). Conclusion: Tumor differentiation could be a predictive factor for tumor recurrence in patients who have undergone curative resection for stage I or II NSCLC.

• Genomics & Informatics
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• v.15 no.4
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• pp.114-122
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• 2017

It is becoming increasingly clear that eukaryotic genomes are subjected to higher-order chromatin organization by the CCCTC-binding factor/cohesin complex. Their dynamic interactions in three dimensions within the nucleus regulate gene transcription by changing the chromatin architecture. Such spatial genomic organization is functionally important for the spatial disposition of chromosomes to control cell fate during development and differentiation. Thus, the dysregulation of proper long-range chromatin interactions may influence the development of tumorigenesis and cancer progression.

• International Journal of Oral Biology
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• v.43 no.3
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• pp.133-140
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• 2018

Resveratrol (3,4',5,-trihydroxystilbene), a phytoalexin present in grapes, exerts a variety of actions to reduce superoxides, prevents diabetes mellitus, and inhibits inflammation. Resveratrol acts as a chemo-preventive agent and induces apoptotic cell death in various cancer cells. However, the role of resveratrol in odontoblastic cell differentiation is unclear. In this study, the effect of resveratrol on regulating odontoblast differentiation was examined in MDPC-23 mouse odontoblastic cells derived from mouse dental papilla cells. Resveratrol significantly accelerated mineralization as compared with the control culture in differentiation of MDPC-23 cells. Resveratrol significantly increased expression of ALP mRNA as compared with the control in differentiation of MDPC-23 cells. Resveratrol significantly accelerated expression of Col I mRNA as compared with the control in differentiation of MDPC-23 cells. Resveratrol significantly increased expressions of DSPP and DMP-1 mRNAs as compared with the control in differentiation of MDPC-23 cells. Treatment of resveratrol did not significantly affect cell proliferation in MDPC-23 cells. Results suggest resveratrol facilitates odontoblast differentiation and mineralization in differentiation of MDPC-23 cells, and may have potential properties for development and clinical application of dentin regeneration materials.