• Title/Summary/Keyword: Cancer development

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Recent Advances in Understanding the Mechanisms of Particulate Matter-mediated Ocular Diseases (미세먼지에 의한 안구질환 발병 연구 동향)

  • Lee, Hyesook;Choi, Yung Hyun
    • Journal of Life Science
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    • v.30 no.8
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    • pp.722-730
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    • 2020
  • As one of the most serious health risk factors, air pollution can no longer be ignored. Particulate matter (PM) is an important and harmful component of air pollution that originates from a variety of sources. Numerous recent studies have linked PM to a range of conditions including cancer, cardiovascular, respiratory, and skin disease. The eye, despite being directly exposed to air pollution, has been investigated in very few of these studies. In this review, we describe the evidence from in vitro and in vivo studies, as well as epidemiological investigations, that supports the association between exposure to PM and the development of ocular conditions such as surface and retinal disease and glaucoma. Based on the results of previous studies, we suggest that PM exposure can lead to oxidative stress, inflammation, autophagy, and, ultimately, ocular surface disease. Nevertheless, almost no studies focus on ocular surface damage from PM while some epidemiological and clinical studies report on the posterior of the eye. However, the underlying pathological mechanisms in the posterior following PM exposure have yet to be identified, and further studies are therefore warranted of the ocular surface as well as the posterior part of the eye.

Phospholipase D Activity is Elevated in Hepatitis C Virus Core Protein-Transformed NIH 3T3 Mouse Fibroblast Cells (C형 간염바이러스의 core 단백질에 의해 암화된 쥐의 섬유아세포에서 phospholipase D 효소활성의 증가)

  • Kim, Joonmo;Jung, Eun-Young;Jang, Kyung-Lib;Min, Do-Sik
    • Journal of Life Science
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    • v.13 no.5
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    • pp.551-558
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    • 2003
  • Hepatitis C Virus (HCV) is associated with a severe liver disease and increased frequency in the development of hepatocellular carcinoma. Overexpression of HCV core protein is known to transform fibroblast cells. Phospholipase D (PLD) activity is commonly elevated in response to mitogenic signals, and PLD has been also reported to be overexpressed and hyperactivated in some human cancer. The aim of this study was to understand how PLD can be regulated in HCV core protein-transformed NIH3T3 mouse fibroblast cells. We observed that in unstimulated state, basal PLD activity was higher in NIH3T3 cells overexpressing HCV core protein than in vector-transfected cells. Although expression of PLD and protein kinase C (PKC) in core protein-transformed cells was similar with that of control cells, phorbol 12-myristate 13-acetate (PMA), which is known to activate PKC, stimulated significantly PLD activity in core protein-transformed cells, compared with that of the control cells. PLD activity assay using PKC isozyme-specific inhibitor, and PKC translocation experiment showed that PKC-$\delta$ was mainly involved in the PMA-induced PLD activation in the core-transformed cells. Taken together, these results suggest that PLD might be implicated in core protein-induced transformation.

DNA Microarray Analysis of the Gene Expression Profile of Activated Human Umbilical Vein En-dothelial Cells. (올리고 마이크로어래이를 이용한 활성화된 인간 제대 정맥 내피세포의 유전자 발현 조사)

  • 김선용;오호균;이수영;남석우;이정용;안현영;신종철;홍용길;조영애
    • Journal of Life Science
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    • v.14 no.5
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    • pp.874-881
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    • 2004
  • Angiogenesis has been implicated in progression of inflammation, arthritis, psoriasis, atherosclerosis as well as tumor growth and metastasis. Intensive studies have been carried out to develop a strategy for cancer treatment by blocking angiogenesis. During angiogenesis, endothelial proliferation and migration essentially occurs upon activation. In this study, we compared the expression profiles of human umbilical endothelial cells activated by incubating in vitro in the rich medium containing several growth factors, and non-activated ones. cDNA targets derived from total RNAs of HUVEC activated for 13 h in M199 medium containing endothelial cell growth supplement, 20% fetal bovine serum, and heparin, after reaching 70~80% confluency, or non-activated, were hybridized onto oligonucleotide microarrays containing 1,8864 genetic elements. Unsupervised hierarchical clustering analysis resulted in two subgroups on dendrogram exhibiting activated and non-activated HUVECs. We then extracted 122 outlier genes which were shown to be up-regulated or under-expressed by at least 2-folds in activated HUVECs. Among these, 32 annotated genes were up-regulated and 38 were down-regulated in activated HUVECs. Interestingly, genes involved in cell proliferation, motility, and inflammation/ immune response were up-regulated in activated HUVEC, whereas genes for cell adhesion or vessel morphogenesis/function were down-regulated. Unexpectedly, the expression of genes well-characterized as angiogenesis markers was not changed except Eph-B4, which was down-regulated about 4 folds. 52 unknown genes were also up- or down-regulated. Therefore, these results could provide an opportunity to targeting new vascular molecules for the development of anti-angiogenic molecules.

Drug Release from Thermosensitive Liposomes by High-Intensity Focused Ultrasound (고강도 집속 초음파에 의한 온도민감성 리포솜으로부터 약물 방출)

  • Jeon, Ye Won;Cho, Sun Hang;Han, Hee Dong;Shin, Byung Cheol
    • Journal of the Korean Chemical Society
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    • v.58 no.6
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    • pp.575-579
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    • 2014
  • Development of liposomes has been actively studied for effective delivery of drug at tumor site. However, despite their preferential accumulation at tumor site, the therapeutic efficacy of such liposomal drug has been limited because of low drug release. Therefore, we developed a temperature-sensitive liposome (TSL), which can be made to maximize release of drug by external stimulation such as ultrasound. Doxorubicin (DOX) as a model drug was encapsulated into TSL by a pH gradient method. The particle size of the TSL was $142.0{\pm}6.24nm$. Surface charge was $-10.55{\pm}1.12mV$. Release of drug from TSLs was up to 80% within 15 min at over $42^{\circ}C$ measured by fluorescence intensity. Cytotoxicity of released DOX from TSLs with ultrasound was highly increased compared to TSLs without ultrasound. Taken together, we demonstrate that temperature sensitive drug release from TSLs with ultrasound, which may be useful for cancer therapy to increase drug concentration at tumor site by external stimulation.

Sex-related Differences in Rat Hepatic Cytochromes P450 Expression Following Treatment with Phenobarbital or 3-Methylcholanthrene

  • Lee, Yoon-Sook;Park, Sang-Shin;Kim, Nak-Doo
    • Archives of Pharmacal Research
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    • v.15 no.1
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    • pp.78-86
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    • 1992
  • The induction of hepatic cytochromes P450 and metabolic effects have been examined in male and female Sprague-Dawley rats following treatment with either phenobarbital or 3-methylcholanthrene. Hepatic cytochrome P450 levels were higher in males than in females by ~40%. Treatment of male and female rats with phenobarbital or 3-methylcholanthrene resulted in an ~1.6 and 2-fold increase, respectively, in heptic microsomal cytochrome P450 levels in both sexes, relative to untreated animals. Immunoblot analyses were performed to compare sex-related changes in P450 levels. Hepatic P45IIB1 levels in males were greater than those in females following phenobarbital treatment. 3-Methylcholanthrene-induced male hepatic microsomes exhibited greater levels of P450 females failed to exhibit a band. Mab PCN 2-13-1 against P-45-IIIA recognized an intense in uninduced microsomes from female rats. The levels of P450IIIA in males were increased 2 to 3-fold following treatment with phenobarbital, while the increase of IIIA levels in females by phenobarbital was minimal, as monitored by immunoblot analysis. Solid phase radiommunoassay using monoclonal antibodies supported the results of immunoblot analysis. Phenobarbital treatment caused a 6.5-fold increase in the monoclonal iantibody binding to IIBI in males, whereas treatment of females with phenobarbital resulted of IA levels by 3-methylcholanthrene was also greater in females than in males (10-vs. 8-fold) although the levels of induced IA were comparable inboth sexes, as assessed by radiommunoassay. Radioimmunoassay also showed that hepatic IIEI level was 1.5-fold higher in males than in females and that either phenobarbital or 3-methylcholanthrene treatment caused 80% to 40% decrease in IIEL levels, relative to control, in both sexes. Sex-related metabolic activities were examined in hepatic microsomes. Hexobarbital hydroxylase activity was 2-to 3-fold higher in uninduced microsomes from males than that from females. This hydroxylase activity was increased 2-and 3-fold in males and females, respectively, following phenobarbital treatment, as compared to controls. Addition females produced 64% and 84% inhibition of hexobarbital oxidation, respectively. Aryl hydrocarbon hydroxylase activity was increased -12 and 26-fold in males and females respectively. Following phenobarbital treatment, as compared to controls. Addition of anti-P450IIB1 antibody to phenobarbital-induced hepatic microsomes from males and females produced 64% and 84% inhibition of hexobarbital oxidation, respectively. Aryl hydrocarbon hydroxylase activity was increased -12 and 26 fold in males and females, respectively, following 3-methylcholanthrene treatment relative to controls. The anti-P-450IA antibody inhibitable rate of aryl hydrocarbon hydroxylase activity was comparable in both sexes following 3-methylcholanthrene treatment relative to controls. The anti-P450LA antibody inhibitable rate of aryl hydrocarbon hydroxylase activity was comparable in both sexes following 3-methylcholanthrene treatment (-70%). These results demonstrate that levels of hepatic P450IIB1 or P450IA are greater in male than in female for untreated, phenobarbital-or-3-methylcholanthrene treated rats. In addition, the relative for untreated phenobarbital-or 3-methylcholanthrene treated rats. In addition, the relative increase of phenobarbital-or 3-methylcholanthrene treated rats. In addition, the relative increase of phenobarbital-or 3-methylcholanthrene treated rats. In addition, the relative increase of P450IIB1 or IA phenobarbital or 3-methylcholanthrene is more significant in females.

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Difference in Lung Functions according to Genetic Polymorphism of Tobacco Substance Metabolizing Enzymes of Korean Smokers (한국인 흡연자들의 담배 물질 대사 효소의 유전자 다형성에 따른 폐기능 차이)

  • Kang, Yun-Jung
    • Journal of Convergence for Information Technology
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    • v.10 no.5
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    • pp.134-142
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    • 2020
  • This study aimed to determine whether there was a difference in lung functions of smokers according to the presence of carcinogenic genetic-metabolizing enzymes by comparing the results of lung functions and the presence of genetic metabolizing enzymes that metabolize tobacco substances. To achieve this, 31 smokers without no illness and no psychiatric history were selected (28 males and 3 females); they were aged 20 to 27 years and were physically and mentally healthy students attending K University. Their lung functions were measured, and gene polymorphisms of cytochrome P-450 1A1 (CYP1A1) related to metabolic activation of tobacco components and gene polymorphism of tumor protein 53 (TP53) related to lung cancer were analyzed. As a result, the mean values of lung function of TT and Arg / Arg without genetic mutations were the highest, and ANOVA analysis of CYP1A1 and lung functions showed that the P-value of FVC was 0.049, which was different between groups. In other words, there is no high mutation in Cytochrome P-450 1A1 (CYP1A1) gene, which is associated with the metabolic activation of tobacco components. In other words, In the absence of the mutant Cytochrome P-450 1A1 (CYP1A1) gene, which is associated with the metabolic activation of tobacco components, the value of FVC was high.

Expression of Vascular Endothelial Growth Factor and Angiogenesis in the Thyroid Tumor (갑상선 종양에서 VEGF(Vascular Endothelial Growth Factor)의 발현과 신생혈관생성)

  • Tae Kyung;Lee Yong-Seop;Park In-Beom;Seo In-Seok;Lee Hyung-Seok;Oh Young-Ha;Park Yong-Soo;Ahn Yoo-Heon
    • Korean Journal of Head & Neck Oncology
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    • v.20 no.2
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    • pp.128-134
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    • 2004
  • Background and Objectives: Angiogenesis is the process of new blood vessel development from preexisting vessel. Angiogenenesis has been considered to be essential for the growth and expansion of a solid tumor. Vascular endothelial growth factor (VEGF), known as one of the most important vascular permeability factors, induces proliferation of endothelial cells, stiumulates angiogenesis, and increases vascular permeability. Several recents reports have documented that VEGF overexpression is associated with poor clinical outcomes in many maligmancies. The aims of this study were to determine whether microvessel density and VEGF expression are related to clinicopathologic factors such as age, sex, tumor size, tumor stage, and prognostic factors and to evaluate the relationship between VEGF expression and angiogenesis in benign and malignant thyroid tumors. Materials and Methods: The subjects were 65 patients (27 with papillary carcinoma, 27 with adenomatous hyperplasia, 11 with follicular adenoma) who underwent thyroidectomy from 1995 to 2001. Imuunohistochemistry was used to detect VEGF expression and microvessel density (MVD) in paraffin-embedded thryoid tumor specimens. Results: The intensity of the VEGF expression did not show stastically difference between benign and malignant thyroid tumors. There was no apparent correlation between VEGF expression and age, tumor size, T stage or scores of the AGES, AMES and MACIS systems. The neo-microvessel density was higher in the maligant tumor than the benign tumors. Also, higher neo-microvessel density was associated with metastases of the lymph nodes and scores of the AMES and AGES systems. Conclusion: Our results suggest that neo-microvessel vessel density may be a significant prognostic factor in the thyroid papillary carcinoma. But the VEGF expression does not appear to be an significant independent prognostic factor for thyroid papillary carcinoma.

Chemopreventive Effects of Garlic Extracts on Rat Colonic Aberrant Crypt Foci Induced by 1,2-Dimethylhydrazine (1,2-Dimethylhydrazine에 의해 유발된 Colonic Aberrant Crypt Foci에 대한 마늘추출물의 암예방효과)

  • Kim, Tae-Myoung;Ryu, Jae-Myun;Kwon, Hyun-Jung;Hwang, In-Guk;Ban, Jung-Ok;Jeong, Heon-Sang;Hong, Jin-Tae;Kim, Dae-Joong
    • Toxicological Research
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    • v.23 no.4
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    • pp.321-330
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    • 2007
  • Garlic (Allium sativum L.) with the food supplement material and medicine was used traditionally in Asia and Europe. Epidemiological studies revealed that the intake of garlic reduced incidences of various cancer including digestive system. The present study was designed to investigate the effect of garlic ethanol extract on the development of colonic aberrant crypt foci (ACF) induced by 1,2-dimethylhydrazine (DMH) in male F344 rats. Five-week-old rats were given four times for two weeks to subcutaneous injections by DMH (30 mg/kg body weight) to induce ACF. The animals were divided into groups that fed diet containing garlic ethanol extract at five different doses (0.1, 0.2, 0.5, 2, 5%), respectively, animals were evaluated for the total number of ACF and total aberrant crypts (AC) per colon detected from methylene blue-stained rat colon. ACF were formed in animals in DMH-treated group. The feeding suppressed potently the appearance ACF in the colon of rats. Especially, fed diet containing garlic ethanol extract at intermediate dose (0.5%) significantly reduced the number of ACF and AC per colon (p < 0.05). Garlic ethanol extract inhibited DMH-induced overexpression of Activator Protein-1 (AP-1) and ${\beta}-catenin$ genes related to cell proliferation that also upregulated the expression of p21Waf1/Cip1 mRNA, a cell cycle-regulating gene. These results suggested that garlic ethanol extract may inhibit ACF formation, ${\beta}-catenin$ gene as the early preneoplastic marker of malignant potential in the process of colon carcinogenesis.

Effects of Synchronicity of Carbohydrate and Protein Degradation on Rumen Fermentation Characteristics and Microbial Protein Synthesis

  • Seo, J.K.;Kim, M.H.;Yang, J.Y.;Kim, H.J.;Lee, C.H.;Kim, K.H.;Ha, Jong K.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.3
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    • pp.358-365
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    • 2013
  • A series of in vitro studies were carried out to determine i) the effects of enzyme and formaldehyde treatment on the degradation characteristics of carbohydrate and protein sources and on the synchronicity of these processes, and ii) the effects of synchronizing carbohydrate and protein supply on rumen fermentation and microbial protein synthesis (MPS) in in vitro experiments. Untreated corn (C) and enzyme-treated corn (EC) were combined with soy bean meal with (ES) and without (S) enzyme treatment or formaldehyde treatment (FS). Six experimental feeds (CS, CES, CFS, ECS, ECES and ECFS) with different synchrony indices were prepared. Highly synchronous diets had the greatest dry matter (DM) digestibility when untreated corn was used. However, the degree of synchronicity did not influence DM digestibility when EC was mixed with various soybean meals. At time points of 12 h and 24 h of incubation, EC-containing diets showed lower ammonia-N concentrations than those of C-containing diets, irrespective of the degree of synchronicity, indicating that more efficient utilization of ammonia-N for MPS was achieved by ruminal microorganisms when EC was offered as a carbohydrate source. Within C-containing treatments, the purine base concentration increased as the diets were more synchronized. This effect was not observed when EC was offered. There were significant effects on VFA concentration of both C and S treatments and their interactions. Similar to purine concentrations, total VFA production and individual VFA concentration in the groups containing EC as an energy source was higher than those of other groups (CS, CES and CFS). The results of the present study suggested that the availability of energy or the protein source are the most limiting factors for rumen fermentation and MPS, rather than the degree of synchronicity.

Efficacy of Lens Shielding Device to Prevent Cataract with Radiotherapy for Orbit or Ocular Adnexal Tumor (안와 및 안부속기 종양의 방사선치료에서 백내장의 예방을 위한 렌즈보호 장치의 효용성)

  • Cho, Jung-Keun;Cho, Hyun-Sang;Han, Tae-Jong
    • The Journal of the Korea Contents Association
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    • v.7 no.12
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    • pp.139-144
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    • 2007
  • Radiotherapy which is the most effective for orbit lymphoma has been used increasingly due to the increase of orbit or ocular adnexal tumor patients. Curative effects and convalescence have been being more satisfied thanks to remarkable development of cancer chemotherapy and medical treatments, but side effects such as cataract, dry eye and retinopathy still break out. Thus, in this study, a Lens Shielding Device (LSD hereafter) was designed to prevent occurring of cataract due to radiation therapy for orbit lymphoma and its efficacy through dosimetry were evaluated. And in this paper, its manufacturing process was also explained. LSD is composed of a cover body covering the lens and a side fixing part supporting the cover body. To measure radiation, the patient therapy conditions were simulated and the measurement of the radiation was conducted with Thermo Luminescence Detector (TLD) and Markus chamber. The average TLD value was 5.7% and the TLD value and Markus chamber value were acquired as 4.2% and 5.1% respectively at 6 mm depth where zero lens center was located. Only 1.5Gy ($300Gy{\times}\;5%$) or 5% of total 30Gy with 9 MeV electron beam is estimated to affect on patient's lens. That is smaller dose than the threshold value of cataract (2GY) or the value (5Gy) that was reported to cause cataract in clinical conditions. Thus, these findings suggest that LSD be very useful for prevention of cataract during radiotherapy for malignant lymphoma of orbit and ocular adnexa. Furthermore, it might be possible to reduce patient's discomfort caused by alien substances and to make it easier to fix the device with customized manufacturing manners.