• Journal of Life Science
• /
• v.30 no.8
• /
• pp.661-671
• /
• 2020

The resistance of cancer cells to anti-cancer drugs is the leading cause of chemotherapy failure. The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been gradually extended to cancer treatment through combination with anti-cancer drugs. In the current study, we investigated whether NSAIDs including celecoxib (CCB), 2,5-dimethyl celecoxib (DMC), and ibuprofen (IBU) could enhance the cytotoxic effects of imatinib and TNF-related apoptosis inducing ligand (TRAIL) on human cancer cells. We found that the NSAIDs potentiated TRAIL and imatinib cytotoxicity against human hepatocellular carcinoma (HCC) cell lines SNU-354, SNU-423, SNU-449, and SNU-475/TR and against leukemic K562 cells with high level of CD44 (CD44^highK562), respectively. More specifically, CCB induced endoplasmic reticulum stress via up-regulation of ATF4/CHOP which is associated with the induction of autophagy against HCC and CD44^high K562 cells. NSAID-induced autophagic activity accelerated TRAIL cytotoxicity of HCC cells through up- and down-regulation of DR5 and c-FLIP, respectively. The NSAIDs also potentiated imatinib-induced cytotoxicity and apoptosis through down-regulation of markers in CD44^highK562 cells that express a stemness phenotype. Our results suggest that the ability of NSAIDs to induce autophagy could enhance the cytotoxicity of TRAIL and imatinib, leading to a reverse resistance to these drugs in the cancer cells. In conclusion, NSAIDs in combination with low-dose TRAIL or imatinib may constitute a novel clinical strategy that maximizes therapeutic efficacy of each drug and effectively reduces the toxic side effects.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.21 no.5
• /
• pp.544-550
• /
• 1992

This study was investigated on the antitumor effects of protein-polysaccharide fraction(PPF) extracted from seaweeds such as sea-lettuce and gonpi toward sarcoma-180 cells. In the PPF extracted from these seaweeds, the polysaccharide contents of sea-lettrce and gonpi were 52.20% and 48.16%, respectively. The highest levels of constituents monosaccharides found in seaweeds was fructose. The major amino acids were aspartic acid, glutamic acid, glycine and cystein. The solid tumor growth inhibition showed the highest level of 64.55% when 50mg/kg sea-lettuce was administerated. The life prolongation effect was 18.31% at 50mg/kg of gonpi. In the effects of immunologic activity, when 50mg/kg sea-lettuce was administrated, the number of circulating leucocyte showed the highest level (65.11%). The number of total peritoneal exudate cells of the sea-lettuce administerated group was increased significantly in comparison with the control group. The hematological analysis of the experimental group was similar with that of the control group.

• Journal of the Korea Academia-Industrial cooperation Society
• /
• v.17 no.1
• /
• pp.152-158
• /
• 2016

Glutamate is one of the major excitatory neurotransmitters in the central nervous system of vertebrates. Human GDH (hGDH) is the enzyme that regulates the glutamate metabolism and its expression is higher in the brains of schizophrenia patients than in normal subjects. This study examined the changes in the hGDH enzymatic activity caused by antipsychotic drugs (haloperidol, risperidone, (${\pm}$)-sulpride, chlopromazine hydrochloride, melperone, (${\pm}$)butaclamol, domperidone, clozapine) related to schizophrenia. First of all, hGDH isozymes (hGDH1, hGDH2) were synthesized by genetic recombination. As a result of the enzyme assay, haloperidol, (${\pm}$)-sulpride, melperone and clozapine had an inhibitory effect on the hGDH isozymes. In addition, haloperidol showed a non-competitive inhibition against the substrate, 2-oxoglutarate. In contrast, it showed an uncompetitive inhibition against another substrate, NADH. The inhibitory effect of haloperidol on hGDH2 was abolished by the presence of L-leucine, an allosteric effector of hGDH, but by not other antipsychotic drugs. These results revealed the inhibition of enzyme activity by psychotropic drugs in hGDH isoenzymes (hGDH1 and hGDH2) and the possibility that haloperidol may be used to regulate the GDH activity and glutamate concentration in the central nervous system.

• Journal of Life Science
• /
• v.33 no.9
• /
• pp.754-765
• /
• 2023

Exosomes are a type of extracellular vesicle containing proteins and messenger and microRNAs; they are secreted by all cell types. Once released, exosomes are selectively taken up by other cells adjacent or at a distance, releasing their contents and reprogramming the target cells. Since exosomes are natural vesicles produced by cells as small sizes, it is generally accepted that exosomes have a non-toxic nature and non-immunogenic behaviors. Recently, exosomes have elicited scientific attention as drug delivery vehicles to the central nervous system. The central nervous system has a blood-brain barrier that makes it difficult for drugs to penetrate. Thus, the blood-brain barrier has been a major obstacle to the development of drugs for treating neurodegenerative diseases. However, accumulating evidence suggests that exosomes can cross the blood-brain barrier primarily through transcytosis. Consequently, exosomes are expected to become a new delivery vehicle that can cross the blood-brain barrier and deliver drugs into the brain parenchyma. In addition, since different types of exosomes are secreted depending on the cell type and disease state, exosomes can also be utilized as biomarkers for the diagnosis of diseases in the central nervous system. In this review, we summarized recent research trends on exosomes, including clinical trials as biomarkers and treatment options for diseases in the central nervous system.

• Journal of Chest Surgery
• /
• v.37 no.8
• /
• pp.672-683
• /
• 2004

Background: The treatment results of the advanced lung carcinoma is not satisfactory with the present therapeutic modalities: surgical resection, anti-cancer chemotherapy, and radiotherapy or combination therapy. To predict the prognosis of the non-small-cell lung carcinoma, TNM classification has been was as the basic categorization; however, it has been not satisfactory. It is necessary to consider the causes and the prognosis of the lung carcinoma from another points of view rather the conventional methods. We intended to find out the relationship between the major apoptotic factor, p53 gene and the prognosis of the patient with lung carcinoma. Material and Method: Three hundreds and fifty-nine patients with lung carcinoma who underwent surgery were analysed. We observed p53 protein accumulated in the cellular nuclei. The p53 protein was detected by immuno-histo-chemical method. We collected information of the patient retrospectively. Result: p53 protein densities were observed in 40% in average as a whole. The protein density was 44 percent in man, 25 percent in woman, 49 percent in the squamous cell carcinoma, and 38 percent in the adenocarcinoma. There were significant correlations between the p53 protein density and the mortality in the squamous cell carcinoma (p=0.025), follow-up duration in TNM stage I group (p=0.010), and follow-up duration in the lobectomy patient group (p=0.043), and tumor cell differentiation (p=0.009). p53 protein densities were significantly different between the lobectomy and the pneumonectomy group (p=0.044). Conclusion: The authors found that p53 protein had some correlations with the prognosis of the lung cancer partially in some factors. We suggest the p53 protein density could be used as a marker of prognosis in the non-small-cell lung carcinoma.

• Journal of Acupuncture Research
• /
• v.21 no.4
• /
• pp.237-249
• /
• 2004

유근피는 혈액청정작용과 혈액순환에 영향을 주는 성분으로서 골 손상의 처방전으로 자주 사용된다. 현재까지 유근피가 골재형성에 미치는 영향은 약리학적으로 불확실하였다. 이에 저자들은 본 연구에서 유근피를 약침액으로 제조하여 유근피 약침액이 골세포에 미치는 영향을 in vitro에서 연구하였다. 방법으로 인체의 골아전구세포osteoprecursor cells (OPC-1)를 각각의 다른 유근피 농도를 함유한 매체내에서 부화시키고 그에 따른 세포증식을 연구하였으며, 유근피 약침액의 농도가 $100{\mu}g/ml$ 미만이었을 때 OPC-1의 증식량은 증가되었다. 그러나 농도가 $180{\mu}g/ml$을 초과하였을 때는 약물의 독성에 의해서 OPC-1의 증식량이 확연히 억제되었다. 대부분의 처치에서 세포들이 cyclooxygenase-2 (Cox 2) 단백질에 대해서 매우 명백한 발현을 보여줬다. 배양과정 중에 유근피 약침액 농도 최소치인 $1.0{\mu}g/ml$에서 최대치인 $500{\mu}g/ml$까지 경미하게 강화된 띠를 나타내었다. 이와 같은 실험의 결과로 볼 때 유근피 약침액은 골세포의 증식활동, alkaline phosphatse(ALP) 활동 및 total protein 분비의 증가와 골세포내에서의 농도의존적 약침액 투여량에 따른 OPC-1의 독특한 type I collagen 합성에 직접적인 억제작용을 주는 것을 관찰할 수 있으므로 추후 이와 유사한 실험을 통한 보다 발전적인 연구가 이루어져야 한다고 사료되었다.

• Journal of Korean Medical classics
• /
• v.18 no.4 s.31
• /
• pp.134-144
• /
• 2005

통과대해역병재${\ulcorner}$동의수세보원(東醫壽世保元)${\lrcorner}$중적상관내용여현대의학적비교연구(中的相關內容與現代醫學的比較硏究), 가류추출여하결론(可類推出如下結論): ${\ulcorner}$내경(內經)${\lrcorner}$중출현적해역병, 재척부혹맥적진단법급자침적류오인식상(在尺部或脈的診斷法及刺針的謬誤認識上), 언급도해역병. 저시인위파열(這是因爲把熱), 혈소(血少), 비토허(脾土虛), 상화작위료기근원적연고(相火作爲了其根源的緣故). 해역병적증상시‘한불한(寒不寒), 열불열(熱不熱), 약불약(弱不弱), 장불장(壯不壯)’급(及)‘소삭, 행산, 불능거(不能去)’ 재(在)${\ulcorner}$동의수세보원(東醫壽世保元)${\lrcorner}$중칭위‘기병가유(其病可愈)’, 이종현대의학적각도진행연구결과(而從現代醫學的角度進行硏究結果), 인위유류사여말초신경적병증(認爲有類似與末稍神經的病證). 종현대의학적원인래간(從現代醫學的原因來看), 유어단백질(由於蛋白質)-능량적영양결핍화유생소급미량원소적부족(能量的營養缺乏和維生素及微量原素的不足), 출현말초신경병증(出現末稍神經病證). 재(在)${\ulcorner}$동의수세보원(東醫壽世保元)${\lrcorner}$적약물중(的藥物中), 야유능량화유생소급미량원소등성분(也有能量和維生素及微量原素等成分), 소이인위대태양인적처방(所以認爲對太陽人的處方), 종영양학각도진행분석연구시유가치적(從營養學角度進行分析硏究是有價値的).

• Biomolecules & Therapeutics
• /
• v.2 no.1
• /
• pp.47-53
• /
• 1994

The methylation response as well as the level of methyl donor substance, 5-adenosyl-L-methionine (SAM) has been suggested to be related to hepatotoxicity including hepatocarcinogenesis. But direct correlation between protein methylation and hepatotoxicity has not been established to the present. To observe relationship between protein methylation and short-term hepatotoxicity induced by chemical substances, the activities of protein methylase I and II (PM I, PM II) were examined in cytosolic fraction of SD rat treated orally with acetaminophen(AA), $\alpha$-naphtyl-isothiocyanate (ANIT) and tetracycline (TC) that was known to produce necrosis, cholestasis and steatosis respectively. To evaluate the degree of hepatotoxicity induced by each chemicals, we observed the serum levels of indicative parameters and histopathological alteration. In AA treated group, the activities of PM I were increased at 6, 12 hours after administration, prior to the appearance of the hepatotoxicity by clinical parameters. It was suggested that the levels of PM I were related with the initial stage of hepatotoxic mechanism induced by AA. In ANIT treated group, though most of clinical parameters were significantly increased at 24, 48 hours after administration, the activity of PM I was not changed, indicating that ANIT induced hepatotoxicity was not coupled to protein methylation.

• Biomolecules & Therapeutics
• /
• v.2 no.1
• /
• pp.59-64
• /
• 1994

The water extract of pilose antler of Cervus nippon var. mantchuricus (WEC) was investigated in respect of its effect on ceruloplasmin and $\alpha$$_1$-cysteine protease inhibitor (CPI), which are acute-phase proteins showing increased synthesis following inflammatory stimulus in rat. Ceruloplasmin and CPI were spectrophotometrically determined by the oxidase activity and the inhibitory activity on papain, respectively, and their changes in the concentrations in plasma or serum were examined after oral administration of 0.04% WEC to rats during 7 days following inflammation by subcutaneous injection of turpentine oil or lipopolysaccharide (LPS). WEC suppressed the maximum increases in ceruloplasmin and CPI on the 4th day after injection of turpentine oil, but the suppression in ceruloplasmin was more potent than that in CPI. On inflammation by LPS the suppression of the maximum increase in ceruloplasmin by WEC was found on the 2nd day, but the result was less significant from that obtained by the treatment with turpentine oil. Administration of WEC for at least 4 days was required to suppress the maximum increase in ceruloplasmin due to inflammation by turpentine oil. When WEC was administered to rats after injection of turpentine oil, a high dosage (0.36% of WEC) was requisite for the suppression on the maximum increase in ceruloplasmin.

• Biomolecules & Therapeutics
• /
• v.4 no.1
• /
• pp.46-50
• /
• 1996

Inhibition of the growth of human cancer cells by proteins secreted from 373-L1 cells was investigated in the present study. The growth of human cancer cells was inhibited by co-culture with 373-L1 cells under 10% FBS and DME, DME, GIT and serumless medium, respectively. The conditioned medium of cultured 373-L1 cells under serumless medium was concentrated 100-fold through an ultrafiltration cell with a 10,000 molecular weight cutoff at 4$^{\circ}C$ under positive pressure using nitrogen(373-L1 EM). 373-L1 EM inhibited the growth of HeLa, Hep G 2, KHOS-Np, A43l and MCF-7 cells. 3T3-L1 EM was purified with FPLC, DEAE-ion exchange chromatography and phenyl-sepharose chromatography. The major protein of 373-L1 EM has a molecular weight of 66,000-68,000 in SDS-PAGE analysis. The results suggest that the inhibitory activity of 373-L1 EM appears to be due to some protein(m.w.66,000-68,000) secreted by 373-L1 cells.