• Title/Summary/Keyword: Pathway

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The Role of Cyclooxygenase Metabolites in the Pathogenetic Mechanism of Endotoxin-Induced Acute Lung Injury in Domestic Pigs (내독소에 의한 돼지의 급성 폐손상에서 Cyclooxygenase 대사물의 역할에 관한 연구)

  • Yoo, Chul-Gyu;Jeong, Ki-Ho;Choi, Hyung-Seok;Lee, Hyuk-Pyo;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Kim, Keun-Youl;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.39 no.1
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    • pp.42-54
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    • 1992
  • Background:It has been suggested that the cyclooxygenase metabolites play an important role in changes of early hemodynamic parameters in the endotoxin-induced acute lung injury. But there have been many debates about their role in the late increase of alveolar-capillary permeability, and it is not known whether they act directly or indirectly through oxygen free radicals which have been known to be produced during the metabolic process of cyclooxygenase pathway. So we performed this study to identify the pathogenetic role of cyclooxygenase metabolites in the endotoxin-induced acute lung injury in domestic pigs. Method: We infused endotoxin into 8 domestic pigs; endotoxin only (n=3), and pretreatment with indomethacin (n=5). We observed the sequential changes in hemodynamic parameters, the concentration of plasma oxidized glutathione (GSSG) in pulmonary arterial and venous blood, and albumin content in bronchoalveolar lavage fluid (BALF). Results: 1) While cardiac output decreased, mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference increased over phase 1 (0-2hr) and phase 2 (2-4.5hr) by endotoxin, indomethacin attenuated the decrease in cardiac output during phase 1 and increase in mean pulmonary arterial pressure, pulmonary vascular resistance, and alveolar-arterial oxygen difference during both phases. 2) The increase in plasma GSSG content during phase 2 was not attenuated by indomethacin. 3) The content of BALF albumin was significantly lower in indomethacin groups than that of endotoxin group. Conclusion: These results suggest that it is likely that cyclooxygenase metabolites have an effect on endotoxin-induced acute lung injury during both phases probably through direct action.

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Jejunal Pouch Interposition (JPI) after Distal Gastrectomy in Patients with Gastric Cancer (위암 환자에서 원위부 위절제 후 공장낭 간치술)

  • Jeon, Hae-Myung;Kim, Wook;Hur, Hoon;Lee, Joon-Hyun;Won, Jong-Man
    • Journal of Gastric Cancer
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    • v.4 no.4
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    • pp.242-251
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    • 2004
  • Purpose: Recently, because of the increasing numbers of early gastric cancer patients and improvements in their survivals, greater attention has been directed towards the quality of life and nutritional status of gastric cancer patients after surgery. However, conventional reconstructions, Billroth- I, -II (B-I and B-II) or Roux-en-Y, have proven to have certain limitations, such as a small reservoir, and a malabsorption for iron, fat, calcium, and carotene. To overcome these limitations, we used a jejunal pouch interposition(JPI) after a distal gastrectomy not only to substitute for the small reservoir but also to maintain a physiologic pathway for ingested foods. Materials and Methods: A total of 196 gastric cancer patients who underwent a distal gastrectomy between March 2001 and February 2004 were divided into 3 groups: JPI group (n=100), B-I group (n=29), and B-II group (n=67). We assessed the patient's nutritional status, gastric emptying time, and gastrofiberscopic findings. Results: The percents of body weight loss at 6 months, 1 year, and 2 years postoperatively in the JPI group ($5.14\%,\;3.01\%,\;2.37\%$) were significantly less than those of the conventional B-I ($8.41\%,\;6.69\%,\;5.90\%$) and B-II groups ($7.50\%,\;7.65\%,\;5.86\%$) (P=0.011, 0.000, 0.013). The laboratory findings showed no significant differences between the 3 groups, except for a higher total protein level in the JPI group after 6 months postoperatively. Especially, stage I and II cancers in the JPI group showed much higher total protein levels after 1 year postoperatively. The gastric emptying times in the $\^{99m}$Tc- semisolid scans at 6 months, 1 year, and 2 years postoperatively were 102.5, 83.1, and 58.1 minutes in the JPI group, 95.5, 92.0, and 58.5 minutes in the B-I group, and 53.9, 69.1, and 50.2 minutes in the B-II group, respectively. Also, the symptomatic gastric stasis detected with a gastrofiberscope during the early postoperative period (6 months) was gradually improved. Conclusion: From a nutritional aspect, a jejunal pouch interposition after a distal gastrectomy could be an alternative reconstruction method, especially in stage I and II gastric cancer patients, in spite of the longer operation time and the probable delayed gastric emptying.

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Beneficial Effects of Acanthopanax senticosus Extract in Type II Diabetes Animal Model via Down-Regulation of Advanced Glycated Hemoglobin and Glycosylation End Products (제2형 당뇨 동물모델에서 가시오가피 추출물의 당화혈색소 및 최종당화산물 억제를 통한 혈당조절 효과)

  • Kwon, Han Ol;Lee, Minhee;Kim, Yong Jae;Kim, Eun;Kim, Ok-Kyung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.7
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    • pp.929-937
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    • 2016
  • The purpose of this study was to investigate the effect of Acanthopanax senticosus extract (ASE) (ethanol : DW=1:1, v/v) on inhibition of type 2 diabetes using an OLETF rat model via regulation of HbA1c and AGEs levels. Supplementation with ASE 0.1% and 0.5% effectively lowered levels of glucose, insulin, oral glucose tolerance test, and Homa-insulin resistance, suggesting reduced insulin resistance. Blood levels of HbA1c and AGEs were significantly reduced in a dose-dependent manner. As oxidative stress plays a key role in accelerating production of HbA1c and AGEs, which worsen symptoms of type 2 diabetes, levels of malonaldehyde and pro-inflammatory cytokines were measured. Lipid peroxidation in both blood and liver tissues was significantly reduced, and induction of pro-inflammatory cytokines interleukin-${\beta}$ and tumor necrosis factor-${\alpha}$, which elevate production of HbA1c and AGEs, was inhibited (P<0.05). To evaluate the possible cellular events after AGEs receptor activation, genetic expression of protein kinase C (PKC)-${\delta}$ and transforming growth factor (TGF)-${\beta}$ was measured by real-time polymerase chain reaction. Supplementation with both ASE 0.1% and 0.5% significantly inhibited mRNA expression of PKC-${\delta}$ and TGF-${\beta}$, indicating that ASE may have beneficial effects on preventing insulin-resistant cells or tissues from progressing to diabetic complications. Taken together, ASE has potential to improve type 2 diabetes by inhibiting insulin resistance and protein glycosylation, including production of HbA1c and AGEs. Anti-oxidative activities of ASE are a main requisite for reducing production of HbA1c and AGEs and are also related to regulation of the PKC signaling pathway, resulting in suppression of TGF-${\beta}$, which increases synthesis of collagen, prostaglandin, and disease-related proteins.

EFFECTS OF HYDROQUINONE ON NEOPLASTIC TRANSFORMATION OF HUMAN EPITHELIAL CELLS IN CULTURE (Hydroquinone이 인체 상피세포의 발암화에 미치는 영향)

  • Sohn, Jung-Hee;Kim, Chin-Soo
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.32 no.3
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    • pp.218-228
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    • 2010
  • Components of dental resin-based restorative materials are reported to leach from the filling materials even after polymerization. Hydroquinone (HQ) is one of the major monomers used in the dental resin and is known as a carcinogen. Thus, carcinogenic risk of HQ leaching from the dental resin becomes a public health concern. The present study attempted to examine the carcinogenic potentials of HQ on the human epithelial cell, which is the target cell origin of the most of oral cancers. Cytotoxicity of HQ was observed above 50${\mu}M$ as measured by LDH assay, indicating a relatively low toxicity of this substance in human epithelial cells. The parameters of neoplastic cellular transformation such as cell saturation density, soft agar colony formation and cell aggregation were analyzed to examine the carcinogenic potential of HQ. The study showed that 2-week exposure of HQ showed the tendency of increase in the saturation density and the significant enhancement of soft agar colony formation at the highest dose, 50 ${\mu}M$ only. It is suggested that HQ has a weak potential of carcinogenicity. When cells were treated with HQ and TPA, a well-known tumor promoter, the parameters of neoplastic cellular transformation was significantly increased. This result indicates that the potential risk of carcinogenicity from HQ is largely dependent upon the presence of promoter. Exposure of 50 ${\mu}M$ HQ increased the time-dependent apoptosis as measured by the ELISA kit. This concentration coincides with a dose of neoplastic transformation, indicating a possible link between apoptosis and HQ-induced cellular transformation. Hydroquinone generated Reactive Oxygen Species (ROS) which was evidenced by the treatment of antioxidants such as trolox and N-acetyl cysteine and the GSH depleting agent, BSO. Antioxidants blocked the generation of ROS and the GSH depleting agent, BSO dramatically increased the ROS production. Since HQ is known to increase ROS production thru activation of transcriptional factor such as c-Myb and Pim-1, it is speculated that ROS generation by HQ plays a role in the activation of oncogene, which may lead to neoplastic transformation. In addition, ROS is involved in the alteration of signal transduction, which regulates the apoptosis in many cellular systems. Thus, ROS-mediated apoptosis may be involved in the HQ-induced carcinogenic processes. Protein kinase C (PKC) is known to play pivotal roles in neoplastic transformation of cells and its high expression is often found in a variety of types of tumors including oral cancer. PKC translocation of PKC-${\alpha}$ was observed following HQ exposure. Altered signaling system may also play a role in the transformation process. Taken together, HQ leached from the dental resin does not pose a significant threat as a cancer causing agent, but its carcinogenic potential can be significantly elevated in the presence of promoter. The mechanism of HQ-induced carcinogenesis involved ROS generation, apoptosis and altered signaling pathway. The present study will provide a valuable data to estimate the potential risk of HQ as a carcinogen and understand mechanism of HQ-induced carcinogenesis in human epithelial cells.

The Characteristics Asian Dust Observed in Japan Deflecting the Korean Peninsula (2010. 5. 22.-5. 25.) (한반도를 돌아 일본에서 관측된 황사의 특징 (2010년 5월 22일-5월 25일))

  • Ahn, Bo-Young;Chun, Young-Sin
    • Journal of the Korean earth science society
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    • v.32 no.4
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    • pp.388-401
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    • 2011
  • Asian dust was observed a total of 66 times in the springtime during the period from 2002 to 2010, with 26 cases in March, 23 cases in April and 17 cases in May. This study investigates a Asian dust episode that occurred during the period from 22 to 25 May 2010, based on synoptic weather patterns, wind vector at 850 hPa, relative humidity at 1000 hPa, Jet streams and wind vector at 300 hPa, PM10 concentration in Korea and satellite imagery. In this case, Asian dust originated on 22 May along the rear of a developing low pressure system in Mongolia. The Asian dust was then transported southeastward and bypassed the Korea peninsula from 23 to 24 May, before reaching Japan on 25 May. Jet streams on 24 May bypassed the Korean peninsula and induced the development of a surface low pressure centered over the peninsula. The resulting air flow was critical to the trajectory of the Asian dust, which likewise bypassed the Korean peninsula. 72-hour backward trajectory data reveal that the Shandong Peninsula and the East China Sea were the points of origin for the air flows that swept through the Japanese sites where Asian dust was observable to the naked eay. The Asian dust pathway is ascertained by horizontal distribution of the Asian dust of RGB imagery from MODIS satellites which captured the Asian dust moving over the Shandong Peninsula, the East China Sea, and northwest of the Kyushu region in Japan. Since the synoptic pattern and the transport way of the Asian dust case are far from typical ones, which Asian dust forecasting technique has long been based on, this study can be good example of exceptional Asian dust pattern and it will be used for more accurate Asian dust forecasting.

Prediction of Changes in Habitat Distribution of the Alfalfa Weevil (Hypera postica) Using RCP Climate Change Scenarios (RCP 기후변화 시나리오 따른 알팔파바구미(Hypera postica)의 서식지 분포 변화 예측)

  • Kim, Mi-Jeong;Lee, Heejo;Ban, Yeong-Gyu;Lee, Soo-Dong;Kim, Dong Eon
    • Korean journal of applied entomology
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    • v.57 no.3
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    • pp.127-135
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    • 2018
  • Climate change can affect variables related to the life cycle of insects, including growth, development, survival, reproduction and distribution. As it encourages alien insects to rapidly spread and settle, climate change is regarded as one of the direct causes of decreased biodiversity because it disturbed ecosystems and reduces the population of native species. Hypera postica caused a great deal of damage in the southern provinces of Korea after it was first identified on Jeju lsland in the 1990s. In recent years, the number of individuals moving to estivation sites has concerned scientists due to the crop damage and national proliferation. In this study, we examine how climate change could affect inhabitation of H. postica. The MaxEnt model was applied to estimate potential distributions of H. postica using future climate change scenarios, namely, representative concentration pathway (RCP) 4.5 and RCP 8.5. As variables of the model, this study used six bio-climates (bio3, bio6, bio10, bio12, bio14, and bio16) in consideration of the ecological characteristics of 66 areas where inhabitation of H. postica was confirmed from 2015 to 2017, and in consideration of the interrelation between prediction variables. The fitness of the model was measured at a considered potentially useful level of 0.765 on average, and the warmest quarter has a high contribution rate of 60-70%. Prediction models (RCP 4.5 and RCP 8.5) results for the year 2050 and 2070 indicated that H. postica habitats are projected to expand across the Korean peninsula due to increasing temperatures.

Immunohistochemical Study of Phosphatase and Tensin Homolog Deleted on Chromosome Ten in Gefitinib Treated Nonsmall Cell Lung Cancer Patients (폐암 조직에서의 PTEN 발현 정도와 Gefitinib의 반응율과의 관계)

  • Lee, Sung Yong;Lee, Ju Han;Jung, Jin Yong;Lee, Kyoung Ju;Lee, Seung Hyeun;Kim, Se Joong;Lee, Eun Joo;Hur, Gyu Young;Jung, Ki Hwan;Jung, Hye Cheol;Lee, Sang Yeub;Kim, Je Hyeong;Shin, Chol;Shim, Jae Jeong;In, Kwang Ho;Kang, Kyung Ho;Yoo, Se Hwa
    • Tuberculosis and Respiratory Diseases
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    • v.58 no.5
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    • pp.473-479
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    • 2005
  • Background : Gefitinib targets the epidermal growth factor receptor r(EGFR), and Gefitinib has antitumor activity in patient with non-small cell lung cancer (NSCLC). However, only 10 to 20 percent of patients show a clinical response to this drug, and the molecular mechanisms underlying patient sensitivity to gefitinib are unknown. PTEN (Phosphatase and tensin homolog deleted on chromosome Ten) plays a role for the modulation of the phosphatidylinositol 3-kinase pathway (PI3K), which is involved in cell proliferation and survival, so that it can inhibit cell cycle progression and induce G1 arrest. Therefore, we analyzed the relationship between PTEN expression and gefitinib's responsiveness in patients having advanced non small cell lung cancer that had progressed after previous chemotherapy. Methods : The expression of PTEN was studied by immunohistochemistry in paraffin-embedded tumor blocks that were obtained from 22 patients who had been treated with gefitinib from JAN, 2001 to AUG. 2004. For the evaluation of the relationships between the PTEN expression, the clinical stage and the basal characteristics, those cases that showed the respective antigen expression in >50% of the tumor cells were considered positive. Results : The positive rate of PTEN staining was 55% of the total of 22 patients. There was a significant relationship between the increased expression of PTEN and the response group (p=0.039). However, there was no significant relationship between the expression of PTEN and other clinicopathologic characteristics. Conclusion: The expression of PTEN in patients with advanced non small cell lung cancer that has progressed after previous chemotherapy may play a role in gefitinib's responsiveness.

Electrocardiographic and Echocardiographic Characterisitics of Wolff-Parkinson-White Syndrome in Preschool Children (학동전 아동에서 Wolff-Parkinson-White 증후군의 심전도 소견에 따른 유형 및 심초음파 소견)

  • Chu, Jeoung Min;Sim, Hyun Sup;Cho, Soo Chul;Joo, Chan Uhng
    • Clinical and Experimental Pediatrics
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    • v.45 no.9
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    • pp.1097-1105
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    • 2002
  • Purpose : This study was conducted to estabilish the prevalence, clinical features and relationship between ECG findings and echocardiographic findings of Wolff-Parkinsion-White(WPW) syndrome in asymptomatic preschool children. Methods : An electrocardiographic screening study was performed on 77,824 preschool children in Jeonbuk province from April, 1999 to August, 2001. Patients with WPW syndrome underwent echocardiographic study. Results : Twenty three patients with WPW syndrome were discovered by electrocardiographic screening of preschool children. The prevalence rate was 2.9 per 10,000 preschool children and there was no significant sexual difference. Two patients had a history of symptoms related to tachyarrythmia. According to the ECG classification of Rosenbaum et al., five patients were type A and 18 were type B. Utilizing the criteria of Gallagher et al, right anterior, 12 patients; right anteiror paraseptal, four patients; left anteiror, three patients. Nineteen of 23 patients underwent echocardiographic study. Four of five patients with type A WPW syndrome had abnormal early systolic anterior motion of left ventricular posterior wall. Twelve of 14 patients with type B had abnormal interventricular septal motion characterized by early sytolic posterior motion immediately after inscription of the delta wave. Conclusion : The prevalence rate of preschool children in Jeonbuk province was 2.9/10,000. By the classification according to the electrocardiographic findings, the accessory pathway location was dominant right side than left side. In the echocardiographic study, type A WPW syndrome showed abnormal left ventricular posterior wall motion and type B WPW showed abnormal interventricular septal motion.

Anti-Inflammmatiry Effects of Nerium indicum Ethanol Extracts through Suppression of NF-kappaB Activation (NF-κB 활성 저해를 통한 협죽도 에탄올 추출물의 항염증 효능)

  • Kim, Tae-Hwan;Ko, Seog-Soon;Park, Cheol;Park, Sang-Eun;Hong, Sang-Hoon;Kim, Byung-Woo;Choi, Yung-Hyun
    • Journal of Life Science
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    • v.20 no.8
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    • pp.1221-1229
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    • 2010
  • Nerium indicum, an India-Pakistan-originated shrub belonging to the oleander family, is reported to possess many pharmacological activities including cardiac muscle stimulation, and anti-diabetes, anti-angiogenesis, anti-cancer and neuro-protective activities. However, the anti-inflammatory properties of N. indicum were unclear. In this study, we investigated the effects of ethanol extract of the N. indicum leaf and stem (ENIL and ENIS) on the expression of anti-inflammatory mediators in U937 human pre-monocytic cell models. In U937 cells stimulated with phorbol 12-myristate-13-acetate (PMA), pre-treatment with ENIS significantly inhibited the expression of both cyclooxygenase-2 (COX-2) mRNA and protein, which are associated with inhibition of the release of prostaglandin $E_2\;(PGE_2)$, whereas the inhibitory effects appeared weakly in ENIL. Moreover, ENIS significantly attenuated PMA-induced IkappaB ($I{\kappa}B$) degradation and suppressed elevated nuclear factor kappa B (NF-${\kappa}B$) nuclear translocation. Taken together, these findings provide important new insights that N. indicum exhibits anti-inflammatory properties by suppressing the transcription of pro-inflammatory cytokine genes through the NF-kB signaling pathway.

Effects of Mifepristone and Tamoxifen on Calcium Modulation in DU-145 Prostate Cancer Cells (DU-145 전립선 암세포에 있어서 mifepristone과 tamoxifen이 칼슘조절에 미치는 영향)

  • Kim, Yeo-Reum;Kim, Byeong-Gee
    • Journal of Life Science
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    • v.20 no.9
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    • pp.1324-1331
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    • 2010
  • Mifepristone (MIF) and Tamoxifen (TAM) have been used in the treatment of prostate cancer and breast cancer for more than a decade. MIF can induce apoptosis in both AR-positive and negative prostate cancer cells. Because of its pleiotropic ligand-receptor properties, TAM exerts cytotoxic activity in estrogen (ER)-positive and various ER.negative cancer cells. However, the molecular mechanisms of these two substances are not yet clear. In the present work, we report that the cytotoxic effects of MIF and TAM are due to the modulation of intracellular $Ca^{2+}$ level in DU-145, androgen-insensitive cells. When the cells were treated with micromolar concentrations of either MIF or TAM, the growth and viability were significantly decreased in a dose- and time-dependent manner. The apoptosis induced by MIF or TAM was further proved and analyzed by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS). In the cells cultivated in a normal 1.5 mM $Ca^{2+}$ medium, both MIF and TAM also induced an increase of the intracellular $Ca^{2+}$ level in a dose-dependent fashion. Since a change in calcium level could not be found in cells of the $Ca^{2+}$-free medium, the increase of intracellular $Ca^{2+}$ level might be due to an increase in extracellular calcium uptake. Our results show that the apoptotic effect was more prominent in TAM treatment compared to MIF treatment in DU-145 cells. The above findings might be due to the difference in the uppermost pathways of apoptosis induced by either MIF or TAM. When we checked the level of procaspase-8 activation, TAM showed minor level of activation, as opposed to MIF, which exerted strong activation. In both treatments, the levels of anti-apoptotic protein Bcl-2 decreased, and pro-apoptotic protein Bax level increased more than 2-fold. The activation of caspase-3, a key protease enzyme in the downstream pathway of apoptosis, was much higher in the cells treated with TAM, compared to the MIF treatment. The overall apoptotic activity shown in the present work was closely related to intracellular $Ca^{2+}$ concentration levels. Therefore, the cytotoxic activity induced by MIF and TAM might have been due to intracellular calcium modulation.