• Title/Summary/Keyword: lethal factor

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The Effect of Combination of Radiation with 5-Fluorouracil on Mouse Jejunal Crypt Cells (5-Fluorouracil 투여가 마우스 공장 소낭선세포의 방사선조사 효과에 미치는 영향)

  • Huh, Seung-Jae;Park, Charn-Il
    • Radiation Oncology Journal
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    • v.3 no.2
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    • pp.87-93
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    • 1985
  • The interaction of radiation and 5-Fluorouracil (5-FU) on mouse jejunal crypt cells was studied using the microcolony survival assay. 150mg/kg of 5-FU was injected intraperitoneally 15 minutes before irradiation and 6 hours after irradiation. Jejunal crypt cells of mouse survived more when 5-FU was given 15 minutes before irradiation than giving it 6 hours after irradiation. The mean lethal doses (Do) of each of irradiation alone group, 5-FU injection group of 15 minutes preceding irradiation, and 5-FU injection group of 6 hours post irradiation were, 135, 135, and 114 rad respectively. The dose effect factor (DEF) of each of 5-FU injection groups of 15 minutes preceding irradiation and of 6 hours post irradiation were 1.13 and 1.27

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Intravenous Single and Two Week Repeated Dose Toxicity Studies of Rice Cells-derived Recombinant Human Granulocyte-Macrophage Colony Stimulating Factor on Rats

  • Ji, Jung-Eun;Lee, Jung-Min;Choi, Jong-Min;Choi, Young-Hwa;Kim, Seok-Kyun;Ahn, Kyong-Hoon;Lee, Dong-Hoon;Kim, Ha-Hyung;Han, Kyu-Boem;Kim, Dae-Kyong
    • Toxicological Research
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    • v.23 no.4
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    • pp.383-389
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    • 2007
  • Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) regulates proliferation and differentiation of hematopoietic progenitor cells and modulates function of the mature hematopoietic cells. In the previous study, we reported that hGM-CSF could be produced in transgenic rice cell suspension culture, termed rhGM-CSF. In the present study we examined the single and repeated dose toxicity of rice cells-derived hGM-CSF in SD rats. During single dose toxicity study for 7 days, there were no any toxic effects at any dose of from 10 to $1000{\mu}g/kg$. The lethal dose ($LD_{50}$) was not found in this range. Moreover, repeated dose toxicity study of 14-days period and at the doses of 50 and $200{\mu}g/kg$ (i. v.) of rhGM-CSF did not show any changes in food and water intake. There were also no significant changes in both body and organ weights between the control and the test groups. The hematological and blood biochemical parameters were statistically not different in all the groups. These results suggest that rhGM-CSF has no toxicity in SD rats.

Fatty Acid Binding Protein 5 (FABP5) Promotes Aggressiveness of Gastric Cancer Through Modulation of Tumor Immunity

  • Mei-qing Qiu;Hui-jun Wang;Ya-fei Ju;Li Sun;Zhen Liu;Tao Wang;Shi-feng Kan;Zhen Yang;Ya-yun Cui;You-qiang Ke;Hong-min He;Shu Zhang
    • Journal of Gastric Cancer
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    • v.23 no.2
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    • pp.340-354
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    • 2023
  • Purpose: Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. Materials and Methods: We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). Results: Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokine-cytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. Conclusions: These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.

Association between Impulsivity and Medical Lethality of Suicide Attempts among Suicide Attempters (자살시도자들에서 충동성과 자살시도의 의학적 치명도와의 관계)

  • Park, Ji Won;Suh, Kyung Hoon;Son, Kyung Hoon;Han, Jae Hyun;Jeon, Yeong Ju;Jung, Yu Jin;Lee, Won Joon;Seong, Su Jeong;Han, Chang Hwan;Cho, Gyu Chong;Hwang, Jae Yeon
    • Korean Journal of Biological Psychiatry
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    • v.25 no.4
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    • pp.118-124
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    • 2018
  • Objectives Although impulsivity has long been thought as an important factor influencing suicidal behaviors, it is unknown whether impulsivity increases the risk of dying from suicidal behaviors and what specific component among constructs of impulsivity contributes to the risk of dying among suicide attempters. Methods To elucidate the association between impulsivity and medical lethality of suicide attempt among suicide attempters, we consecutively recruited 46 suicide attempters who visited an emergency room of a general hospital located in a metropolitan area, Seoul, Republic of Korea, due to suicide attempts and consented to participate in this study. Then we assessed medical lethality with the Beck Lethality Scale (LS) and impulsivity with the Korean version of the Barratt Impulsiveness Scale-11-Revised (BIS). Demographic variables were obtained from medical records and structured social work reports for suicide attempters. Results Although total scores of the BIS did not correlate with LS scores, only the scores of self-control, that is one of the Barrett's six theoretical constructs of impulsivity in which the higher score indicates less self-control and more impulsivity, had a significant positive correlation with scores of LS (p = 0.003). The association remained significant after adjusting for variables known to affect suicide lethality such as job status, recent alcohol consumption, diagnosis of depressive disorders, and having a plan for suicide (${\beta}=0.429$, p = 0.009). Conclusions Not impulsivity in general, but poor self-control, in particular, predicts lethal suicidal behaviors among suicide attempters. The degree of self-control should be evaluated when assessing patients with elevated suicide risk, and proper measures should be installed to prevent possible future lethal suicide attempts.

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Safety Evaluation of Recombinant Human Factor VIII(GC-γ AHF) (유전자 재조합 Human Factor VIII(GC-γ AHF)의 안전성에 관한 연구)

  • 김민영;손장원;신민기;배미옥;김현우;최진혁;김준성;문서현;김정현
    • Toxicological Research
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    • v.18 no.1
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    • pp.87-98
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    • 2002
  • This study was conducted to evaluate the safety of a recombinant human Factor VIII(GC-$\gamma$ AHF) manufactured by Korea Green Cross Company with different technology according to the Regulation of Korean Food and Drug Administration (l 998. 12. 3). In acute toxicity test, both genders of Sprague-Dawley rats and Beagle dogs were administered intravenously with GC-$\gamma$ AHF of three doses (3,125, 625 and 125 IU/kg), and single dose of 3,125 IU/kg, respectively. No dead animal and abnormal autopsy findings were found in Control and GC-$\gamma$ AHF treated group. Therefore, the 50% lethal dose ($LD_{50}$) of GC-$\gamma$ AHF was conidered to be higher than 3,125 IU/kg in rats and dogs. In the four weeks repeated intravenous toxicity study, GC-$\gamma$ AHF was administrated intravenosly to both genders of rats and dogs with 3 doses (500, 150, 50 IU/kg). There were neither dead animals nor significant changes of body weights during the experimental Period. In addition, no significant GC-$\gamma$ AHF related changes were found in clinical sign, urinalysis and other finding. Statistically changes were observed in hematological, biochemical and organ weight parameters of treated groups: however these changes were not dose dependent. No histopathological lesion were observed in both control and treated animals. Above data suggest that no observed adverse effect level of test materials in rats and dogs might be over 500 IU/kg/day in this study. In ocular irritation test, any injury on iris, conjunctiva and cornea in rabbits were not observed. The acute ocular irritation index (A.O.I.), mean ocular irritation index (M.O.I.) and Day-7 individual ocular irritation Index (I.O.I.) of GC-$\gamma$ AHF were 0. In the primary skin Irritation test, the primary irritation index (P.I.I.) oj GC-$\gamma$ AHF were 0. Therefore, the GC-$\gamma$ AHF is considered not to have the primary skin and eye toxicity in rabbits. In active systemic anaphylaxis (ASA) test, GC-$\gamma$ AHF and GC-$\gamma$ AHF emulsified with Freund's complete adjuvant (FCA) did not induce any symptom of anaphylactic shock in guinea pigs. In passive cutaneous anaphylxis (PCA) test, after sensitization with antisera of GC-$\gamma$ AHF sensitized mice, blue spots were observed on the hypodermis of back of rats, but diameter of each spot was smaller than 5 mm in each test groups except the positive control group. Based on the results of this study, GC-$\gamma$ AHF is not conidered to have any antigenic potential. In conclusion, at levels of up to 500 IU/kg, GC-$\gamma$ AHF did not produce treatment-related toxicity under the conditions of these acute-, four week repeated-toxicity, primary skin and eye toxicity, and antigenicity test.

Efficacy Study of Osteradionecrosis Using Fibrin and SDF-1 (피브린과 SDF-1을 사용한 방사성뼈괴사의 효용성연구)

  • Hong-Moon, Jung
    • Journal of the Korean Society of Radiology
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    • v.16 no.6
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    • pp.799-805
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    • 2022
  • Radiation therapy of human tissues, including bone tissue, is accompanied by side effects on normal tissues. It has a more lethal effect on stem cells, which play an essential role in tissue regeneration, including the basal cells constituting the tissue. In this study, the mouse parietal model, which implemented an artificial osteoradionecrosis model on the parietal region of the mouse, was artificially defected and then the bone regeneration was tested. In order to overcome the implemented osteoradionecrosis, a fibrin scaffold, widely used as a biomaterial, and stromal cell-derived factor-1 (SDF-1), which is used as a long-term treatment for damaged, were mixed to verify the osteoradionecrosis regeneration effect on the parietal of mouse. In order to expect a synergistic effect in the fibrin scaffolds, a fibrin scaffolds was prepared after maintaining the concentration of SDF-1 (1 ㎍/ml) in the fibrinogen solution. In this study, after artificially creating a osteoradionecrosis model in the parietal region of mouse, fibrin scaffolds were incorporated to analyze the effect of bone regeneration within 4 weeks, the initial stage of bone regeneration. In conclusion, the combined use of these two substances did not show a dramatic regenerative effect in inducing the regeneration of osteoradionecrosis in the parietal region of mouse. However, positive results were obtained that can be maintain the bone regeneration effect environment at the initial stage. Therefore, the combined use of the fibrin scaffold and SDF-1 is considered to be a suitable candidate for the effect of overcoming osteoradionecrosis.

Evaluation of Gene Expression Changes of Serotonin Receptors, 5-HT3AR and 5-HT2AR as Main Stress Factors in Breast Cancer Patients

  • Hejazi, Seyed Hesam;Ahangari, Ghasem;Pornour, Majid;Deezagi, Abdolkhaleagh;Aminzadeh, Saeed;Ahmadkhaniha, Hamid Reza;Akbari, Mohamad Esmail
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.11
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    • pp.4455-4458
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    • 2014
  • Breast cancer is a serious and potentially lethal multi-factor disease among 40-50 aged women in both developed and developing countries. Also, various studies have pointed to roles of neurotransmitters like serotonin in development of cancers, through action on various types of receptors. This study was conducted to evaluate serotonin receptor (5HT2AR and 5HT3AR) genes expression in peripheral blood mononuclear cells (PBMCs) of breast cancer patients in comparison with the healthy people and in the MCF7 cell line. Peripheral blood samples were obtained from 30 patients and 30 healthy individuals. Total RNA was extracted from PBMCs and MCF-7 cells. and 5HT2AR and 5HT3AR were detected by RT-PCR techniques. Finally, serotonin receptor gene expression variation in breast cancer patients and MCF-7 cells were determined by real time-PCR. This latter indicated significant promotion in expression of 5HT3AR and 5HT2AR in PBMCs in breast cancer patients but expression of 5HT2AR in the MCF-7 cell line was significantly decreased. In conclusion, after performing complimentary tests, determine of gene expression changes in serotonin receptors (5HT2AR and 5HT3AR) may be useful as a new approach in treatment of breast cancer based on use of antagonists.

The Study on The Snake Venom (사독(蛇毒)에 대한 문헌적(文獻的) 고찰(考察))

  • Lee, Jin-Seon;Kwon, Gi-Rok
    • Journal of Pharmacopuncture
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    • v.2 no.1 s.2
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    • pp.73-91
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    • 1999
  • This study was carried out to invastigate the researches of Snake Venom and snakes which used in treatment 1. The fist literature that used the snake for treatment is Shin Nong Ben Cao Jing 2. Composition of Snake Venom is consist of Enzymatic proteins ; Phospholipase A(A1-2), Protease, L-amino acid oxidase etc, and Non-enzymatic proteins ; Crotamine(Cytolysin), Proteolytic factor(Hematoxin), Crotoxin(Neurotoxin) etc. 3. Main toxins in Snake Venom are Hematoxin, Cytolysin, Neurotoxin and Cardiotoxin. Lethal dose 50 value of Agkistrodon brevicaudus is $45.87{\mu}g$/18g, Agkistrodon saxatilis is $10.28{\mu}g$/18g, Agkistrodon ussuriensis is $8.68{\mu}g$/18g, therefore Agkistrodon ussuriensis has strongist Snake Venom of all in Korea. 4. Pharmacological actions of Snake Venom are anticoagulation, thrombolytic function, hypotensor etc. 5. Systemic syndromes and signs after snakebite are Dizziness(25.7%), Vomitting(23.1%), Fever(22%), Visual disturbance(18%), Headache(17.7%) and Dyspnea(17.6%), etc. 6. Local syndrome and sign after snakebite is Discoloration(54.2%), Bleeding(20.2%), Bullae(10.7%), Skinulcer(10.8%), etc. 7. Pathological syndromes after snakebite are WBC increase, Urine protein, Urine sugar, Haematuria and elevation of S-GDT, S-GPT etc. These syndromes are leaded by Hematoxin and Cytolysin. 8. Complication signs after snakebite are Cellulitis, Gastritis, Lympoma, Abscess etc. 9. Common function of Viperidae(Agkistrodon acutus or Zaocys dhumnades etc) is expelling the wind(祛風), removing obstruction in the channels(通絡), antipastic function(止痙). And it is used in order to cure hemiparesis, hemiplegia, facial palsy and CVA disease, etc. 10. Using way of snake for medical treatment is various like Herbal alchol therapy, pill, powder and injection etc. The Study on the Snake Venom should be carried out continuously for using of medical treatment.

Application of Apoptogenic Pretreatment to Enhance Anti-tumor Immunity of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)-secreting CT26 Tumor Cells

  • Jun, Do-Youn;Jaffee, Elizabeth M;Kim, Young-Ho
    • IMMUNE NETWORK
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    • v.5 no.2
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    • pp.110-116
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    • 2005
  • Background: As an attempt to develop a strategy to improve the protective immune response to GM-CSF-secreting CT26 (GM-CSF/CT26) tumor vaccine, we have investigated whether the apoptogenic treatment of GM-CSF/CT26 prior to vaccination enhances the induction of anti-tumor immune response in mouse model. Methods: A carcinogeninduced mouse colorectal tumor, CT26 was transfected with GM-CSF gene using a retroviral vector to generate GM-CSF-secreting CT26 (CT26/GM-CSF). The CT26/GM-CSF was treated with ${\gamma}$-irradiation or mitomycin C to induce apoptosis and vaccinated into BALB/c mice. After 7 days, the mice were injected with a lethal dose of challenge live CT26 cells to examine the protective effect of tumor vaccination in vivo. Results: Although both apoptotic and necrotic CT26/GM-CSF vaccines were able to enhance anti-tumor immune response, apoptotic CT26/GM-CSF induced by pretreatment with ${\gamma}$-irradiation (50,000 rads) was the most potent in generating the anti-tumor immunity, and thus 100% of mice vaccinated with the apoptotic cells remained tumor free for more than 60 days after tumor challenge. Conclusion: Apoptogenic pretreatment of GM-CSF-secreting CT26 tumor vaccine by ${\gamma}$-irradiation (50,000 rads) resulted in a significant enhancement in inducing the protective anti-tumor immunity. A rapid induction of apoptosis of CT26/GM-CSF tumor vaccine at the vaccine site might be critical for the enhancement in anti-tumor immune response to tumor vaccine.

Toxicity Assessment of Tetrabromobisphenol A with the Benthic Amphipod, Hyalella azteca (저서 단각류인 Hyalella azteca를 이용한 브롬화방염제 Tetrabromobisphenol A의 독성평가)

  • Lee, Chul-Woo;Song, Sang-Hwan;Kim, Hyun-Mi;Kim, Hak-Joo;Choi, Kyung-Hee;Lee, Moon-Soon
    • Environmental Analysis Health and Toxicology
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    • v.22 no.2 s.57
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    • pp.157-163
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    • 2007
  • Tetrabromobisphenol A (TBBPA) is the most widely used BFR (brominated flame retardants) as a reactive flame retardant in printed circuit boards, and as additive applications in several types of polymers. The purpose of this study is to assess the adverse effects of TBBPA on the benthic amphipod (Hyalella azteca). Results on the acute toxicity of TBBPA using Hyalella azteca showed that NOEC and LOEC are 100mg/kg and 200mg/kg, respectively. In addition, when chronic toxicity of TBBPA was investigated at the concentration ranges between 0.01 to 100mg/kg, it was found that NOECs are $10mg/kg(fecundity){\sim}100mg/kg(viability)$, respectively. Significant fecundity inhibition was appeared at 100mg/kg of TBBPA, however, this concentration did not show severe adverse effect on weight increment. The values of PNEC were determined as 0.1mg/kg (fecundity) and 1mg/kg (lethal effect), respectively, using a safety factor suggested by EU and OECD.