• Journal of Life Science
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• v.17 no.1 s.81
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• pp.110-115
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• 2007

It has been previously described that transcription factor early growth response gene product 1 (EGR-1) functions as a tumor suppressor gene. This study was conducted to demonstrate that EGR-1 induction by phytochemical apigenin and its derivative isovitexin can mediate the growth suppression of the intestinal epithelial tumor cells. Apigenin and isovitexin induced EGR-1 gene expression both in the dose and time-dependent manners. Moreover the induction was relatively late around 9-12 hr after treatment of HCT-116 cells, while several anti-inflammatory agent such as NSAIDS and catechins elicit the ECR-1 gene expression at much earlier time about 1-3 hr after treatment. In terms of signal transduction, ERK1/2 was critical for apigenin-induced EGR-1 gene expression and its promoter activation. When EGR-1 gene expression was blocked with EGR-1 small interference RNA, the cytotoxicity of apigenin in the human epithelial cells was attenuated, suggesting the involvement of EGR-1 in the anti-tumoric activity of apigenin. To link the EGR-1 induction to EGR-1-regulated gene products in colon cancer, NSAID-Activated Gene 1 (NAG-1) was demonstrated to be elevated by apigenin and isovitexin at 24-48 hr after treatment. Taken together, apigenin-activated ERK1/2 mediated EGR-1 gene induction, which was associated with suppression of the cellular viability by apigenin compound.

• The Korea Journal of Herbology
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• v.32 no.5
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• pp.27-38
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• 2017

Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.9
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• pp.4793-4799
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• 2012

Hypoxia is commonly featured during glioma growth and plays an important role in the processes underlying tumor progression to increasing malignancy. Here we compared the gene expression profiles of rat C6 malignant glioma cells under normoxic and hypoxic conditions by cDNA microarray analysis. Compared to normoxic culture conditions, 180 genes were up-regulated and 67 genes were down-regulated under hypoxia mimicked by $CoCl_2$ treatment. These differentially expressed genes were involved in mutiple biological functions including development and differentiation, immune and stress response, metabolic process, and cellular physiological response. It was found that hypoxia significantly regulated genes involved in regulation of glycolysis and cell differentiation, as well as intracellular signalling pathways related to Notch and focal adhesion, which are closely associated with tumor malignant growth. These results should facilitate investigation of the role of hypoxia in the glioma development and exploration of therapeutic targets for inhibition of glioma growth.

• The Journal of Korean Medicine
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• v.17 no.2 s.32
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• pp.227-236
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• 1996

The effect of Ligustrum Lucidum(LL) on the production of nitric oxide (NO) and superoxide by murine peritoneal macrophages were investigated. Stimulation of the cells with LL in the presence or absence of interferon-r(IFN-r) resulted in the increased accumulation of nitrite in the medium. To further examine the mechanism of LL induced. NO Synthesis, we evaluated the secretion of tumor necrosis $factor-{\alpha}(TNF-{\alpha})$ by LL in murine macrophages. Treatment of LL increased the secretion of bioactive $TNF-{\alpha}$ in cultured medium. In addition, LL induced NO production was decreased by the treatment of anti-murine $TNF-{\alpha}$. neutralizing antibodies, indicating that LL induced superoxide production was decreased by the treatment of anti-murine $TNF-{\alpha}$ neutralizing antibodies. These data suggested that LL induced superoxide production was related to $TNF-{\alpha}$ secretion. In conclusion, our results indicates that LL may enhance innate immune response and be applied as a immunoregulating drug improving phagocytosis.

• The Journal of Korean Obstetrics and Gynecology
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• v.35 no.1
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• pp.91-104
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• 2022

Objectives: The purpose of this study is to report the effect of combination treatment of Traditional Korean medicine (TKM) and chemotherapy on a ovarian cancer with lung metastasis patient. Methods: One ovarian cancer with lung metastasis patient was treated by TKM in conjunction with Carboplatin/paclitaxel since Feb. 2020. Repeat cycle every 3 weeks for 6 times. The patient has been treated with TKM at the same time. To evaluate the patient, symptoms were measured by Numeric Rating Scale (NRS), Eastern Cooperative Oncology Group (ECOG) and tumor size was measured by scanning with Computed Tomography (CT). Blood tests including cancer biomarker were conducted during treatment. Adverse events were evaluated by the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), version 5.0. Results: After treatment with Carboplatin/paclitaxel and TKM during 2 months, the size of the ovarian cancer was decreased(Partial Response, PR), size and malignant pleural effusion at right lung disappeared. And no evidence of newly developed metastatic lesions. After 2 months, the tumor response was stable disease while improving the performance and other symptoms. Conclusions: This case provides us conjunctive treatment with Conventional and Eastern medicine may have substantial benefit for patients with end-stage ovarian cancer.

• Journal of Digestive Cancer Research
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• v.10 no.2
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• pp.65-73
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• 2022

A breakthrough in immunotherapy has changed the outlook for metastatic colorectal cancer (mCRC) treatment as the immune surveillance evasion mechanism of tumor cells has been continuously elucidated. Immune checkpoint inhibitors (ICI), such as pembrolizumab, nivolumab, and ipilimumab, which block immune checkpoint receptors or ligands have been approved for the treatment of mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) mCRC based on numerous clinical studies. However, 50% of dMMR/MSI-H mCRC and most mismatch repair proficient/microsatellite stable mCRC remained unresponsive to current immunotherapy. Clinical trials on combination therapy that adds various treatments, such as target agents, chemotherapy, or radiation therapy to ICI, have been actively conducted to overcome this immunotherapy limitation. Further studies on safety and efficacy are needed although several trials presented promising data. Additionally, dMMR/MSI-H, tumor mutation burden, and programmed cell death ligand-1 expression have been studied as biomarkers for predicting the treatment response to immunotherapy, but the discovery and validation of more sensitively predictable biomarkers remained necessary. Thus, this study aimed to review recent studies on immunotherapy in mCRC, summarize the efficacy and limitation of immunotherapy, and describe the biomarkers that predict treatment response.

• Radiation Oncology Journal
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• v.33 no.4
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• pp.294-300
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• 2015

Purpose: To evaluate survival rates and prognostic factors related to treatment outcomes after bladder preserving therapy including transurethral resection of bladder tumor, radiotherapy (RT) with or without concurrent chemotherapy in bladder cancer with a curative intent. Materials and Methods: We retrospectively studied 50 bladder cancer patients treated with bladder-preserving therapy at Keimyung University Dongsan Medical Center from January 1999 to December 2010. Age ranged from 46 to 89 years (median, 71.5 years). Bladder cancer was the American Joint Committee on Cancer (AJCC) stage II, III, and IV in 9, 27, and 14 patients, respectively. Thirty patients were treated with concurrent chemoradiotherapy (CCRT) and 20 patients with RT alone. Nine patients received chemotherapy prior to CCRT or RT alone. Radiation was delivered with a four-field box technique (median, 63 Gy; range, 48.6 to 70.2 Gy). The follow-up periods ranged from 2 to 169 months (median, 34 months). Results: Thirty patients (60%) showed complete response and 13 (26%) a partial response. All patients could have their own bladder preserved. Five-year overall survival (OS) rate was 37.2%, and the 5-year disease-free survival (DFS) rate was 30.2%. In multivariate analysis, tumor grade and CCRT were statistically significant in OS. Conclusion: Tumor grade was a significant prognostic factor related to OS. CCRT is also considered to improve survival outcomes. Further multi-institutional studies are needed to elucidate the impact of RT in bladder cancer.

• Journal of Korean Neurosurgical Society
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• v.58 no.4
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• pp.334-340
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• 2015

Objective : Pineal parenchymal tumors (PPTs) in adults are rare, and knowledge regarding their optimal management and treatment outcome is limited. Herein, we present the clinical results of our series of PPTs other than pineoblastomas managed by stereotactic radiosurgery (SRS) at upfront setting. Methods : Between 1997 and 2014, nine consecutive adult patients with the diagnosis of PPTs, either pineocytoma or pineal parenchymal tumor of intermediate differentiation, were treated with SRS. There were 6 men and 3 women. The median age was 39 years (range, 31-53 years). All of the patients presented with symptoms of hydrocephalus. Endoscopic third ventriculostomy and biopsy was done for initial management. After histologic diagnosis, patients were treated with Gamma Knife with the mean dose of 13.3 Gy (n=3) or fractionated Cyberknife with 32 Gy (n=6). Results : After a mean follow-up of 78.6 months (range, 14-223 months), all patients were alive and all of their tumors were locally controlled except for one instance of cerebrospinal fluid seeding metastasis. On magnetic resonance images, tumor size decreased in all patients, resulting in complete response in 3 patients and partial response in 6. One patient had experienced temporary memory impairment after SRS, which improved spontaneously. Conclusion : SRS is effective and safe for PPTs in adults and can be considered as a useful alternative to surgical resection at upfront setting.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3805-3809
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• 2014

Background: In Mexico, breast cancer (BCa) is the leading type of cancer in women. Cytochrome P450 (CYP450) is a superfamily of major oxidative enzymes that metabolize carcinogens and many antineoplastic drugs. In addition, these enzymes have influence on tumor development and tumor response to therapy. In this report, we analyzed the protein expression in patients with BCa and in healthy women. Links with some clinic-pathological characteristic were also assessed. Materials and Methods: Immunohistochemical analyses were conducted on 48 sets of human breast tumors and normal breast tissues enrolled in Hospital Militar de Especialidades de la Mujer y Neonatologia and Hospital Central Militar, respectively, during the time period from 2010 to 2011. Informed consent was obtained from all participants. Statistical analysis was performed using ${\chi}^2$ or Fisher exact tests to estimate associations and the Mann Whitney U test for comparison of group means. Results: We found a significant CYP3A4 overexpression in BCa stroma and gland regions in comparison with healthy tissue. A significant association between protein expression with smoking, alcoholism and hormonal contraceptives use was also observed. Additionally, we observed estrogen receptor (ER) and progesterone receptor (PR) positive association in BCa. Conclusions: We suggest that CYP3A4 expression promotes BCa development and can be used in the prediction of tumor response to different treatments. One therapeutic approach may thus be to block CYP3A4 function.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.5
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• pp.396-402
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• 2011

Introduction: Epidermal growth factor is a single-chain polypeptide consisting of 53 amino acids with potent mitogenic activity that stimulates the proliferation of a range of normal and neoplastic cells through an interaction with its specific receptor (epidermal growth factor receptor, EGFR). This interaction plays a key role in tumor progression including the induction of tumor cell proliferation. An increased EGFR copy number have been associated with a favorable response to EGFR tyrosine kinase inhibitors therapy. In contrast, K-ras mutations tend to predict a poor response to such therapy. The aim of this study was to determine the correlation between the clinicopathological factors and the up-regulation of EGFR expression and Kras mutations in oral squamous cell carcinoma. Materials and Methods: This study examined the immunohistochemical staining of EGFR, K-ras mutation detection with peptide nucleic acid (PNA)-based real-time polymerase chain reaction (PCR) clamping in 20 specimens from 20 patients with oral squamous cell carcinoma. Results: 1. In the immunohistochemical study of poorly differentiated and invasive oral squamous cell carcinoma, a high level of EGFR staining was observed. The correlation between immunohistochemical EGFR expression and histological differentiation, as well as the tumor size of the specimens was significant (Pearson correlation analysis, significance [r] >0.5, P<0.05). 2. In PNA-based real-time PCR clamping analysis, a K-ras mutation was not detected in all specimens. Conclusion: These findings suggest that the up-regulation of the EGFR may play a role in the progression and invasion of oral squamous cell carcinoma that is, independent of a K-ras mutation.