• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.26 no.1
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• pp.53-58
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• 2000

Treatment of oral cancers with chemotherapeutic agents are evaluated as an effective method for remission to reduce cancer proliferation nowadays. But, minimization of side-effects such as bone marrow suppression, gastrointestinal toxicity and renal damage is another problem to be solved. Thus, a possible approach to develop a clinically applicable chemotherapeutic agents is to screen anticancer activity among traditional medicinal plants which have been used for thousands of years with very low side-effects in orient. In this study we focused on screening anti-oral cancer activities among 14 traditional medicinal plant extracts that revealed anticancer activities on other solid tumors. The results were as follow : 1. Methanol extract of Lepidium apetalum showed the highest anti-oral cancer activity against A253 cells. At concentration of $4{\mu}g/ml$, the cell viability was 48% under our experimental condition. $IC_{50}$ value obtained was $4{\mu}g/ml$. 2. Methanol extract of Coptis japonica and Solanum nigrum were effective on KB cells. Cell viability observed were 62% and 67% at concentration of $4{\mu}g/ml$, and $IC_{50}$ values were $12{\mu}g/ml$ and $10{\mu}g/ml$ respectively. 3. When the methanol extract of Lonicera caerule was combined with $2{\mu}g/ml$ of cisplatin, the anticancer activity was synergistically increased. One hundred ${\mu}g/ml$ of Lonicera caerule showed 92%(alone) or 59%(combined with cisplatin) cell viabilities. $IC_{50}$ value of Lonicera caerule extract against KB cells was reduced from $301{\mu}g/ml$ to $126{\mu}g/ml$ when combined with $2{\mu}g/ml$ of cisplatin. 4. Medicinal plant extracts effective on both A253 and KB cells were Coptis japonica, Lepidium apetalum, Solanum nigrum, Caesalpiniae Lignum, Curcuma aromatica.

• The Korean Journal of Medicine
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• v.93 no.6
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• pp.571-574
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• 2018

Nivolumab is an immune checkpoint inhibitor approved for the treatment of metastatic cancers. Here, we report the case of a 65-year-old male with recurrent renal cell carcinoma. After six cycles of nivolumab treatment, positron emission tomography/computed tomography (PET/CT) was performed to evaluate the response. PET/CT revealed diffuse ground glass opacities in both lungs. He developed a cough, sputum, chills, and a febrile sense. After bronchoscopic bronchoalveolar lavage, pneumocystis pneumonia was finally diagnosed.

• Tuberculosis and Respiratory Diseases
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• v.51 no.4
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• pp.386-389
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• 2001

An endobronchial metastasis is defined as a subsegmental or a more proximal central bronchial metastasis of a nonpulmonary neoplasm in the bronchoscopically visible range. However, the frequencies of endobronchial metastasis range from 2 to 50% of pulmonary metastases from extrathoracic neoplasms by a different definition of an endobronchial metastasis. Primary neoplasms of an endobronchial metastasis including breast cancer, colon cancer, renal cell carcinoma, and ovarian cancer are relatively common. However, an endobronchial metastasis arising from thyroid cancer, parotid gland tumor, bone tumor, bladder cancer, and stomach cancer has only rarely been reported in the literature. Here we report a case of an endobrochial metastases from a hepatocellular carcinoma.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.2
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• pp.159-167
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• 2000

We have synthesized a novel platinum(II) coordination complex containing cis-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-dichloroethane (DCE) as a leaving group. In addition, nitrate was added to improve the water-solubility. A new series of [Pt(cis-DACH)(DCE)] $2NO_3(PC)$ was evaluated for its cytotoxic activity on T-24 and J-82 human bladder carcinoma cells and normal primary cultured kidney cells. PC has demonstrated high levels of cytotoxicity against T-24 and J-82 cells. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells and human renal cortical tissues, determined using the MTT assaying technique, the $[^3H]-thymidine$ uptake and glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum(II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new clinically available anticancer chemotherapeutic agents.

• YAKHAK HOEJI
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• v.44 no.5
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• pp.399-405
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• 2000

We have synthesized a novel platinum (II) coordination complex containing trans-ι-1,2-diaminocyclohexane (DACH) as a carrier ligand and 1,2-bis (diphenylphosphino)ethane (DPPE) as a leaving group. In addition, nitrate was added to improve the water-solubility. A new series of [Pt (trans-ι-DACH) (DPPE)].2NO$_3$(PC) was evaluated for its cytotoxic activity on MKN-45 human gastric adenocarcinoma cells and normal primary cultured kidney cells. PC has demonstrated high levels of cytotoxicity against MKN-45/S, MKN-45/ADR and MKN-45/CDDP cells. The cytotoxicity of PC against rabbit proximal renal tubular cells, human renal cortical cells, and human renal cortical tissues, determined using the MTT assaying technique, the ($^3$H)-thymidine uptake and the glucose consumption tests, was found to be quite less than those of cisplatin. Based on these results, this novel platinum (II) coordination complex appears to be better for improving antitumor activities with low nephrotoxicity and is a valuable lead in the development of new clinically available anticancer chemotherapeutic agents.

• Herbal Formula Science
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• v.23 no.2
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• pp.199-208
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• 2015

Objectives : In the present study, we investigated the effects of ethanol extract of Scutellaria baicalensis (EESB) on the progression of cell cycle in human renal cell carcinoma Caki-1 cells. Methods : The effects of EESB on cell growth and apoptosis induction were evaluated by trypan blue dye exclusion assay and flow cytometry, respectively. The mRNA and protein levels were determined by Western blot analysis and reverse transcription-polymerase chain reaction, respectively. Results : It was found that EESB treatment on Caki-1 cells resulted in a dose-dependent inhibition of cell growth and induced apoptotic cell death as detected by Annexin V-FITC staining. The flow cytometric analysis indicated that EESB resulted in G2/M arrest in cell cycle progression which was associated with the down-regulation of cyclin A expression. Our results also revealed that treatment with EESB increased the mRNA and proteins expression of tumor suppressor p53 and cyclin-dependent kinase (Cdk) inhibitor p21(WAF1/CIP1), without any noticeable changes in cyclin B1, Cdk2 and Cdc2. In addition, the incubation of cells with EESB resulted in a significant increase in the binding of p21 and Cdk2 and Cdc2. These findings suggest that EESB-induced G2/M arrest and apoptosis in Caki-1 cells is mediated through the p53-mediated upregulation of Cdk inhibitor p21. Conclusions : Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent and further studies will be needed to identify the biological active compounds that confer the anti-cancer activity of S. baicalensis.

• Toxicological Research
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• v.34 no.2
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• pp.133-141
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• 2018

Anti-cancer drugs such as cisplatin and doxorubicin are effectively used more than radiotherapy. Cisplatin is a chemotherapeutic drug, used for treatment of various forms of cancer. However, it has side effects such as ototoxicity and nephrotoxicity. Cisplatin-induced nephrotoxicity increases tubular damage and renal dysfunction. Consequently, we investigated the beneficial effect of cynaroside on cisplatin-induced kidney injury using HK-2 cell (human proximal tubule cell line) and an animal model. Results indicated that $10{\mu}M$ cynaroside diminished cisplatin-induced apoptosis, mitochondrial dysfunction and caspase-3 activation, cisplatin-induced upregulation of caspase-3/MST-1 pathway decreased by treatment of cynaroside in HK-2 cells. To confirm the effect of cynaroside on cisplatin-induced kidney injury in vivo, we used cisplatin exposure animal model (20 mg/kg, balb/c mice, i.p., once a day for 3 days). Renal dysfunction, tubular damage and neutrophilia induced by cisplatin injection were decreased by cynaroside (10 mg/kg, i.p., once a day for 3 days). Results indicated that cynaroside decreased cisplatin-induced kidney injury in vitro and in vivo, and it could be used for improving cisplatin-induced side effects. However, further experiments are required regarding toxicity by high dose cynaroside and caspase-3/MST-1-linked signal transduction in the animal model.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3801-3804
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• 2014

Background: The prognostic significance of the neutrophil-to-lymphocyte ratio for progression free survival in patients with metastatic renal cell carcinoma is unclear. Materials and Methods: We retrospectively reviewed 45 patients diagnosed with metastatic RCC previously treated with tyrosine kinase inhibitors from two centers, Akdeniz University Hospital and Afyon Kocatepe University. The prognostic value of the pretreatment neutrophil-tolymphocyte ratio, and other clinical and laboratory parameters were assessed by univariate and multivariate analysis. Results: Median progression free survival (PFS) was 13.9 months [95% CI for HR (6.88-20.91)] and overall survival figure of 16.6 months [95% CI for HR (7.23-26.03)] Univariate analysis revealed that PFS was significantly affected by hemoglobin level [p=0.013 (95% CI for HR (0.71-0.96))], eosinophil count [p=0.031 (95% CI for HR (0.20-0.92))], ratio of neutrophil lymphocytes (NLR) [p=0.007 (95% CI for HR (1.47-11.74))] and calcium level [p=0.006 (95% CI for HR (0.15-0.73))]. However, only NLR [p=0.031 (95% CI for HR (1.15-18.1))] and calcium levels [p=0.018 (95% CI for HR (0.20-18.1))] retained significance with multivariate analysis. Median PFS was 23.9 vs 8.6 months in patients with NLR ${\leq}2$ vs NLR >2 (Log rank; p= 0.040). Conclusions: This study showed that increased pretreatment NLR is an independent prognostic factor for patients with metastatic RCC using tyrosine kinase inhibitors.

• Biomolecules & Therapeutics
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• v.21 no.1
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• pp.1-9
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• 2013

Polyamines, putrescine, spermidine and spermine, are ubiquitous in living cells and are essential for eukaryotic cell growth. These polycations interact with negatively charged molecules such as DNA, RNA, acidic proteins and phospholipids and modulate various cellular functions including macromolecular synthesis. Dysregulation of the polyamine pathway leads to pathological conditions including cancer, inflammation, stroke, renal failure and diabetes. Increase in polyamines and polyamine synthesis enzymes is often associated with tumor growth, and urinary and plasma contents of polyamines and their metabolites have been investigated as diagnostic markers for cancers. Of these, diacetylated derivatives of spermidine and spermine are elevated in the urine of cancer patients and present potential markers for early detection. Enhanced catabolism of cellular polyamines by polyamine oxidases (PAO), spermine oxidase (SMO) or acetylpolyamine oxidase (AcPAO), increases cellular oxidative stress and generates hydrogen peroxide and a reactive toxic metabolite, acrolein, which covalently incorporates into lysine residues of cellular proteins. Levels of protein-conjuagated acrolein (PC-Acro) and polyamine oxidizing enzymes were increased in the locus of brain infarction and in plasma in a mouse model of stroke and also in the plasma of stroke patients. When the combined measurements of PC-Acro, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated, even silent brain infarction (SBI) was detected with high sensitivity and specificity. Considering that there are no reliable biochemical markers for early stage of stroke, PC-Acro and PAOs present promising markers. Thus the polyamine metabolites in plasma or urine provide useful tools in early diagnosis of cancer and stroke.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3729-3734
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• 2013

The aim of this study was to evaluate expression of COX-1 in renal cell carcinoma (RCC) and its prognostic value. mRNA of COX-1 was detected in 42 paired RCC and adjacent normal tissues with quantitative realtime polymerase chain reaction (qRT-PCR). Expression of COX-1 was also evaluated in 196 RCC sections and 91 adjacent normal tissues with immunohistochemistry. Statistical analysis was performed to assess COX-1 expression in RCC and its prognostic significance. The results of qRT-PCR showed mRNA levels of COX-1 in RCC tissues to be significantly higher than that in adjacent normal tissues (p < 0.001). Immunohistochemical assays also revealed COX-1 to be overexpressed in RCC tissues (p < 0.001). Statistical analysis demonstrated high expression of COX-1 was correlated with tumour size (p = 0.002), pathological stage (p = 0.003), TNM stage (p = 0.003, 0.007, 0.027, respectively), and tumour recurrence (p < 0.001). Survival analysis indicated patients with high expression of COX-1 had shorter survival time (p < 0.001), and COX-1 was an independent predictor. This is the first study to reveal overexpression of COX-1 in RRC and point to use as a prognostic marker in affected patients.