• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.44 no.4
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• pp.182-190
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• 2018

Objectives: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. Inconsistency in various histopathologic features for predicting nodal metastasis and overall prognosis and a better understanding of molecular mechanisms of tumourigenesis have shifted the focus to a search for more definitive predictive markers. To identify the role of two immunohistochemical (IHC) markers, E-cadherin and cyclin D1, as predictive markers of aggressiveness in HNSCC and to assess clonal expansion of tumour cells. Materials and Methods: A total of 66 cases of HNSCC with neck node dissection were studied. IHC was performed on primary tumour sections and lymph nodes showing metastatic deposits. Histopathological parameters such as tumour grade and TNM stage together with nodal status were compared according to expression of the two markers. Fischer's chi-square test was used to assess the correlation between the two markers and histopathological parameters. Results: Out of 66 cases studied, 37 showed LN metastasis. Most of the patients were male, and the most common tumour site was buccal mucosa. We found a significant association between loss of E-cadherin and node metastasis (P<0.001) and higher TNM stage (P<0.001). Cyclin D1 overexpression was significantly associated with only nodal metastasis (P=0.007). No significant association with tumour grade was found for either marker. The subgroup of E-cadherin loss with cyclin D1 overexpression was associated with the maximum incidence of nodal metastasis and higher TNM stage, highlighting the importance of using a combination of these two markers. A significant association was noted between the expression of markers at the primary site and at nodal deposits, indicating clonal expansion. Conclusion: A combination of the two markers E-cadherin and cyclin D1 can predict prognosis in HNSCC, although tumour heterogeneity may affect this association in some cases.

• Preventive Nutrition and Food Science
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• v.20 no.3
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• pp.153-161
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• 2015

Matrix metalloproteinases (MMPs) are crucial extracellular matrices degrading enzymes that have important roles in metastasis of cancer progression as well as other significant conditions such as oxidative stress and hepatic fibrosis. Marine plants are on the rise for their potential to provide natural products that exhibit remarkable health benefits. In this context, brown algae species have been of much interest in the pharmaceutical field with reported instances of isolation of bioactive compounds against tumor growth and MMP activity. In this study, eight different brown algae species were harvested, and their extracts were compared in regard to their anti-MMP effects. According to gelatin zymography results, Ecklonia cava, Ecklonia bicyclis, and Ishige okamurae showed higher inhibitory effects than the other samples on MMP-2 and -9 activity at the concentrations of 10, 50, and $100{\mu}g/mL$. However, only I. okamurae was able to regulate the MMP activity through the expression of MMP and tissue inhibitor of MMP observed by mRNA levels. Overall, brown algae species showed to be good sources for anti-MMP agents, while I. okamurae needs to be further studied for its potential to yield pharmaceutical molecules that can regulate MMP-activity through cellular pathways as well as enzymatic inhibition.

• BMB Reports
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• v.38 no.3
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• pp.300-306
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• 2005

Tamoxifen citrate is an anti-estrogenic drug used for the treatment of breast cancer. It showed a degree of hepatic carcinogenesis, when it used for long term as it can decrease the hexose monophosphate shunt and thereby increasing the incidence of oxidative stress in liver rat cells leading to liver injury. In this study, a model of liver injury in female rats was done by intraperitoneal injection of tamoxifen in a dose of 45 mg/kg body weight for 7 successive days. This model produced a state of oxidative stress accompanied with liver injury as noticed by significant declines in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant elevations in TBARS (thiobarbituric acid reactive substance) and liver transaminases; sGPT (serum glutamate pyruvate transaminase) and sGOT (serum glutamate oxaloacetate transaminase) levels. The oral administration of dimethyl dimethoxy biphenyl dicarboxylate (DDB) in a dose of 200 mg/kg body weight daily for 10 successive days, resulted in alleviation of the oxidative stress status of tamoxifen-intoxicated liver injury in rats as observed by significant increments in the antioxidant enzymes (glutathione-S-transferase, glutathione peroxidase and catalase) and reduced glutathione concomitant with significant decrements in TBARS and liver transaminases; sGPT and sGOT levels. The administration of DDB before tamoxifen intoxication (as protection) is more little effective than its curative effect against tamoxifen-induced liver injury. The data obtained from this study speculated that DDB can mediate its biochemical effects through the enhancement of the antioxidant enzyme activities and reduced glutathione level as well as decreasing lipid peroxides.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.169-172
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• 2004

Activity-guided fractionation of the EtOAc-soluble extract of the stems of Couepia ulei, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa 1c1c7 mouse hepatoma cells led to the isolation of two active compounds, a new natural product, erythro-2,3-bis(4-hydroxy-3-methoxyphenyl)-3-ethoxypropan-1-o1 (1), and a known compound, evofolin-B (2), along with five inactive compounds all of known structure, viz., betulinic acid, oleanolic acid, pomolic acid, ($\pm$)-syringaresinol, and ursolic acid. These isolates were identified by analysis of physical and spectral data. Compounds 1 and 2 exhibited QR inducing activity, with observed CD (concentration required to double induction) values of 16.7 and 16.4 $\mu\textrm{M}$, respectively.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.6
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• pp.468-473
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• 2005

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. The molecular mechanisms involved in the development and progression of these carcinomas are not well known. Abnormalities of genomic methylation patterns have been attributed a role in carcinogenesis and local de novo methylation at tumor suppressor loci was held to be involved in silencing of tumor suppressor genes. Using Ms APPCR, we previously isolated a hypermethylated fragment corresponded to the 5' end of TPEF gene from primary liver and lung cancer cells. To confirm the inactivation of TPEF gene by hypermethylation in HNSCC, we investigated correlation between methylation pattern and expression of TPEF in 10 HNSCC cell lines. In methylation analysis such as combined-bisulfite restriction analysis(COBRA) and bisulfite sequencing, only RPMI 2650 showed none methylated pattern and another 9 cell lines showed dense methylation. The TPEF gene expression level analysis using RT-PCR showed that these 9 cell lines had not or significantly low expression levels of TPEF as compared with RPMI 2650. In addition, the increase of TPEF reexpression by 5-AzaC as demethylating agent in 9 cell lines also indicated that TPEF expression was regulated by hypermethylation. These results of this study demonstrate that epigenetic silencing of TPEF gene by aberrant methylation could play an important role in HNSCC carcinogenesis.

• Journal of Ginseng Research
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• v.4 no.1
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• pp.31-39
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• 1980

This study was prepared to observe some enzyme activities in the liver of mice treated with extracts of Ginseng anticancer compound, separated from the petroleum ether extracts by silicic acid chromatography, has the cytotoxic activity against cancer cells. Swiss mice, 72 heads were used (or this experiment and they were divdied into control, test group I and test group If, that test group I was injected crude extract and test group II was injected anticancer compound, while the control group was injected 0.9% NaCl solution. The injections were carried out 1,2,4 and 8 times once a day for 1-8 day, respectively. The liver was removed carefully from the mice at 24 hours after drugs injected, and homogenized at 4$^{\circ}C$ for enzyme study. The activities of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase(GPT) were determined by Reitmen and Frankel method and lactic acid dehydrogenase activity was determined by Wroblewski methods in vitro. The results obtained are summarized as follows; 1. The GOT activity was increased 26%, crude extract and 16%, anticancer compound than those of control at 1st injected groups and decreased gradually according to increase of injection time, at 8th injected groups, the GOT activity was decresed by 16%, crude extract and 12%, anticancer compound. 2. The GPT activity was not changed significantly at 1st and 2nd injected groups, but, at 4th injected groups, the GPT activity was decreased 20%, crude extract and 14%, anticancer compound. While the GPT activity was recovered to normal value at 8th injected groups. 3. At 1st injected groups, the LDH activity was increased 17%, anticancer compound, while those of crude extract was shown normal value. At 2nd injected groups, the LDH activity increased 35yo:, crude extract while those of anticancer compound was showed normal value. And the LOH activity was recovered gradually at 4th and 8th injected groups.

• Journal of Life Science
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• v.17 no.10
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• pp.1381-1386
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• 2007

To elucidate the changes in physiological activities of Scutellariae baicalensis by heating, composition analysis with HPLC and evaluation of physiological activities of extracts were conducted. HPLC analysis of CW(water extract at room temperature) and CHW(heat treated CW) indicated that two distinctive peaks in the HPLC chromatogram were disappeared after boiling and additional peak was newly observed. This observation suggested that certain chemical changed in the extract occurred by heat treatment. In the estimation of physiological activities, CW showed higher ACE inhibiting activity than CHW. In the case of cytotoxic activity against cancer cells, CW exhibited higher activity than CHW against CCL-185. On the other hand, CHW showed higher activity than CW against HeLa, SNU-601 and HepG2. In addition, CHW showed the inhibitory effect on melanogenesis (80% inhibition) while CW did not show any activity.

• Tuberculosis and Respiratory Diseases
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• v.68 no.2
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• pp.93-96
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• 2010

A 23-year old woman was admitted to our hospital with hemoptysis. The chest X-ray showed reticulonodular opacity and multiple cysts throughout the entire lung field. The chest CT scan revealed numerous bilateral cysts with various sizes, some of them with thickened walls. An open lung wedge resection was performed. The resected specimen showed scattered small nodules, 0.3 to 0.6 cm in size. Microscopically, each nodule was composed of atypical glands with an occasional papillary architecture spreading to the alveolar septa, which were morphologically consistent with a papillary adenocarcinoma with a bronchioloalveolar carcinoma growth pattern. Immunochemically, the tumor cells were negative for the S-100 protein. The patient was diagnosed with an adenocarcinoma of the lung. A variety of diseases can produce or mimic multiple, thin-walled cysts in the lung. Lung cancer with multiple cysts is quite rare. Nevertheless, adenocarcinoma should be a diagnostic consideration. We report a case of a multiple cystic adenocarcinoma of the lung.

• IMMUNE NETWORK
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• v.9 no.3
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• pp.98-105
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• 2009

Background: It has been recently noticed that type 2 diabetes (T2D), one of the most common metabolic diseases, causes a chronic low-grade inflammation and activation of the innate immune system that are closely involved in the pathogenesis of T2D. Cordyceps militaris, a traditional medicinal mushroom, produces a component compound, cordycepin (3'-deoxyadenosine). Cordycepin has been known to have many pharmacological activities including immunological stimulating, anti-cancer, and anti-infection activities. The molecular mechanisms of cordycepin in T2D are not clear. In the present study, we tested the role of cordycepin on the anti-diabetic effect and anti-inflammatory cascades in LPS-stimulated RAW 264.7 cells. Methods: We confirmed the levels of diabetes regulating genes mRNA and protein of cytokines through RT-PCR and western blot analysis and followed by FACS analysis for the surface molecules. Results: Cordycepin inhibited the production of NO and pro-inflammatory cytokines such as IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ in LPS-activated macrophages via suppressing protein expression of pro-inflammatory mediators. T2D regulating genes such as $11{\beta}$-HSD1 and PPAR${\gamma}$ were decreased as well as expression of co-stimulatory molecules such as ICAM-1 and B7-1/-2 were also decreased with the increment of its concentration. In accordance with suppressed pro-inflammatory cytokine production lead to inhibition of diabetic regulating genes in activated macrophages. Cordycepin suppressed NF-${\kappa}B$ activation in LPS-activated macrophages. Conclusion: Based on these observations, cordycepin suppressed T2D regulating genes through the inactivation of NF-${\kappa}B$ dependent inflammatory responses and suggesting that cordycepin will provide potential use as an immunomodulatory agent for treating immunological diseases.

• Macromolecular Research
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• v.16 no.6
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• pp.510-516
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• 2008

New antitumor active polymers, poly(methacryloyl-2-oxy-1,2,3-propanetricarboxylic acid-co-exo-3,6-epoxy-l,2,3,6-tetrahydrophthalic acid) [poly(MTCA-co-ETAc)], poly(methacryloyl-2-oxy-l,2,3-propanetricarboxylic acid-co-hydrogen ethyl-exo-3,6-epoxy-l,2,3,6-tetrahydrophthalate) [poly(MTCA-co-HEET)], and poly(methacryloyl-2-oxy-l,2,3-propanetricarboxylic acid-co-a-ethoxy-exo-3,6-epoxy-1,2,3,6-tetrahydrophthaloyl-5-fluorouracil) [poly(MTCA-co-EETFU)] were synthesized and characterized. Their antitumor activity, inhibition of DNA replication and antiangiogenesis were examined. The structures of the polymers were identified by FT-IR, $^1H$ and $^{13}C$-NMR spectroscopy. The number average molecular weights of the fractionated polymers determined by GPC ranged from 9,400 to 14,900, and polydispersity indices were less than 1.7. The in vitro cytotoxicity of these polymers was determined and their antitumor activity was evaluated. The $IC_{50}$ values (the drug concentration at inhibition of 50% tumor growth) indicated that the synthesized polymers were much better inhibitors of cancer cells and showed lower cytotoxicity than the free 5-FU. The in vivo antitumor activity of the conjugates was examined using mice bearing the sarcoma 180 tumor cell line. The life spans (TIC) of the mice treated with the conjugates were higher than those treated with the free 5-FU. In addition, the synthesized conjugates showed excellent antiangiogenic activity based on an embryo chorioallantoic membrane assay.