• Title/Summary/Keyword: treatment related death

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Effect of Autophagy-Related Beclin1 on Sensitivity of Cisplatin-Resistant Ovarian Cancer Cells to Chemotherapeutic Agents

  • Sun, Yang;Liu, Jia-Hua;Jin, Long;Sui, Yu-Xia;Han, Li-Li;Huang, Yin
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.7
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    • pp.2785-2791
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    • 2015
  • The purpose of the study was to determine the effects of autophagy related gene Beclin1 at different levels of expression on the sensitivity of cisplatin-resistant ovarian cancer cells (SKOV3/DDP) to different chemotherapeutics. In pSUPER-Beclin1 transfected cells, real-time fluorescence quantitative RT-PCR and Western blot analysis showed that expression was significantly inhibited. Flow cytometry revealed that the mean fluorescence intensity (MDC), reflecting autophagy, and cells in the G0/G1 phase were markedly reduced. When compared with the blank control group, inhibition of Beclin1 expression in SKOV3/DDP cells not only increased the rate of apoptosis following treatment with chemotherapeutics, but also increased the sensitivity. These findings suggest that Beclin1 expression plays an important role in chemotherapeutic agent-induced death of SKOV3/DDP cells. Inhibition of autophagy related gene Beclin1 expression in SKOV3/DDP cells may increase the rate of apoptosis and elevate the sensitivity to chemotherapeutics.

Mechanism Underlying Curcumin-induced Apoptosis and Cell Cycle Arrest on SCC25 Human Tongue Squamous Cell Carcinoma Cell Line

  • Moon, Jung-Bon;Lee, Kee-Hyun;Kim, In-Ryoung;Kim, Gyoo-Cheon;Kwak, Hyun-Ho;Park, Bong-Soo
    • International Journal of Oral Biology
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    • v.39 no.1
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    • pp.23-33
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    • 2014
  • Several studies have shown that curcumin, which is derived from the rhizomes of turmeric, possesses antimicrobial, antioxidant and anti-inflammatory properties. The antitumor properties of curcumin have also now been demonstrated more recently in different cancers. This study was undertaken to investigate the modulation of cell cycle-related proteins and the mechanisms underlying apoptosis induction by curcumin in the SCC25 human tongue squamous cell carcinoma cell line. Curcumin treatment of the SCC25 cells resulted in a time- and dose-dependent reduction in cell viability and cell growth, and onset of apoptotic cell death. The curcumin-treated SCC25 cells showed several types of apoptotic manifestations, such as nuclear condensation, DNA fragmentation, reduced MMP and proteasome activity, and a decreased DNA content. In addition, the treated SCC25 cells showed a release of cytochrome c into the cytosol, translocation of AIF and DFF40/CAD into the nuclei, a significant shift in the Bax/Bcl-2 ratio, and the activation of caspase-9, caspase-7, caspase-6, caspase-3, PARP, lamin A/C, and DFF45/ICAD. Furthermore, curcumin exposure resulted in a downregulation of G1 cell cycle-related proteins and upregulation of $p27^{KIP1}$. Taken together, our findings demonstrate that curcumin strongly inhibits cell proliferation by modulating the expression of G1 cell cycle-related proteins and inducing apoptosis via proteasomal, mitochondrial, and caspase cascades in SCC25 cells.

Analysis of Cultivator-related Trauma Cases in a Regional Trauma Center in the Rural Area of Gyeongbuk Province

  • Hwang, Ui Kang;Youn, Seok Hwa;Park, Chan Yong
    • Journal of Trauma and Injury
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    • v.30 no.3
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    • pp.80-86
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    • 2017
  • Purpose: To analyze the data of patients who suffered trauma in a cultivator accident and visited the trauma center in rural Gyeongbuk Province. Methods: We retrospectively reviewed the medical records and Korean Trauma Data Bank data of 120 patients who suffered cultivator-related traumas and visited the rural regional trauma center in Gyeongbuk Province from January to December 2015. Results: The age of the patients ranged from 35 to 96 years (mean, 70 years). Ninety-one (75.8%) patients were men, and twenty-nine (24.2%) were women. Most of the patients were in their 70s (46 men [50.5%] and 13 women [44.8%]). In total, 113 patients (94.1%) arrived at the regional trauma center by ground transport and 7 (5.9%) arrived by air transport. Ninety-eight patients (81.7%) were transported to the regional trauma center directly from the scene of the accident, and twenty-two (18.3%) were transferred from another medical institute. The mean time from the accident to arrival at the emergency department was 139 minutes, and only 46 patients (38.3%) arrived within 1 hour. Twelve (10.0%) patients died, including two deaths on arrival and two post- cardiopulmonary resuscitation deaths in the emergency department. All deaths were of male cultivator operators. The causes of death were shock (hypovolemic, traumatic, or septic), subdural hematoma (open), hemothorax, rhabdomyolysis, and pneumonia. Conclusions: As the government - led regional trauma center project is on process, it would be clinically important to summarize the initial outcome of cultivator injuries, which are characteristically found more in regional trauma centers in the rural area, and have high mortality. Based on this study, in the future, it will be necessary to follow up and analyze more number of patients and to construct accurate database about trauma cases related to cultivator in Gyeongbuk region.

Neuroprotective Effect of the Water-insoluble fraction of Roots of Sophora flavescens 70% Ethanolic Extract on Glutamate-Induced Oxidative Damage in Mouse Hippocampal HT22 Cells (고삼 (苦蔘, Sophorae Radix) 70% 에탄올 추출물의 비수용성 분획물의 Heme Oxygenase-1 발현을 통한 뇌세포 보호 작용)

  • Lee, Young-Sook
    • Korean Journal of Pharmacognosy
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    • v.42 no.3
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    • pp.276-281
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    • 2011
  • Oxidative stress or the accumulation of reactive oxygen species (ROS) leads neuronal cellular death and dysfunction, and it contributes to neuronal degenerative disease such as Alzheimer's disease, Parkinson's disease and stroke. Glutamate-induced oxidative injury contributes to neuronal degeneration in many central nervous system (CNS) diseases, such as epilepsy and ischemia. Heme oxygenase-1 (HO-1) enzyme plays an important role of cellular antioxidant system against oxidant injury. The expression of HO-1 has cytoprotective effects in glutamate-induced oxidative cytotoxicity in HT22 cells. The induction of HO-1 is primarily regulated at the transcriptional level, and its induction by various inducers is related to the nuclear transcription factor-E2-related factor 2 (Nrf2). Nrf2 is a master regulator of the antioxidant response. NNMBS008, the water-insoluble fraction of the 70% EtOH extract of roots of Sophora flavescens, showed dominant neuroprotective effects on glutamate-induced neurotoxicity in mouse hippocampal HT22 cells by induced the expression of HO-1 and increased HO activity. In mouse hippocampal HT22 cells, NNMBS008 makes the nuclear accumulation of Nrf2 pathway. In conclusion, the waterinsoluble fraction of the 70% EtOH extract of roots of S. flavescens (NNMBS008) significantly protect glutamate-induced oxidative damage by induction of HO-1 via Nrf2 pathway in mouse hippocampal HT22 cells. These results suggest that these extracts could be the effective candidates for the treatment of ROS-related neurological diseases.

Research on the prevention of legal dispute over 119 rescue team (119구급대의 법적분쟁 예방에 관한 연구)

  • Lim, Jae-Man
    • The Korean Journal of Emergency Medical Services
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    • v.13 no.1
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    • pp.19-33
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    • 2009
  • Purpose : To check the legal relation between rescue team and patient as well as legal responsibility for patient's damage intentionally or erroneously caused by rescue member, a public official, in the performance of relevant job ; to prevent legal dispute over rescue team and to present program for fair settlement of dispute and equitable and feasible burden of damage. Method : First, the legal principle of Civil Law, Criminal Law and Administrative Law related to the theme of this research will be investigated around research by literature. Second, the case of dispute related to rescue team will be introduced. Result: 1. If 119 rescue members as a public official intentionally or erroneously cause damage to patient in the performance of job, they shall bear civil, criminal and administrative responsibility. They shall bear civil responsibility for indemnity for damage due to default or tort. The typical criminal responsibility includes accidental homicide arising out of duty, preparing falsified official document, dereliction of duty, etc. In the administrative side, the state is responsible for indemnity for peculiar status of the rescue member, public official. 2. Though raising civil petition or legal dispute over unsatisfactory rescue service may be reasonable to guarantee the right of nation, such action may cause stress to rescue member as well as may lead to mental shrinking and defensive attitude only to take the basic first aid treatment which has low possibility of mistake instead of active first aid treatment so as to avoid legal responsibility. 3. The program that may prevent legal dispute over 119 rescue team includes expansion of manpower specialized in first aid treatment, enhancement of education on legal environment, development and application of standard job guideline, formation of mutual trust with patient, detailed explanation, preparing and keeping minute record, improvement of the rescue members' ability of first aid treatment and development of medical instruction mode. Conclusion : The best policy is to prevent legal dispute. If it is impossible to basically exclude the possibility of dispute, however, we need to make effort to minimize the occurrence, settle fairly and divide damage equitably and feasibly. To improve the preventible death rate of our first aid system to the level of advanced country, 119 rescue team which is in charge of the stage before hospital needs to positively enforce special first aid by improving the qualitative level of rescue service and to strive to prevent legal dispute that may occur in the process.

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Pro-apoptotic Effect of Pifithrin-α on Preimplantation Porcine In vitro Fertilized Embryo Development

  • Mulligan, Brendan;Hwang, Jae-Yeon;Kim, Hyung-Min;Oh, Jong-Nam;Choi, Kwang-Hwan;Lee, Chang-Kyu
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.12
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    • pp.1681-1690
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    • 2012
  • The aim of this study was to investigate the impact of a reported p53 inhibitor, pifithrin-${\alpha}$ (PFT-${\alpha}$), on preimplantation porcine in vitro fertilized (IVF) embryo development in culture. Treatment of PFT-${\alpha}$ was administered at both early (0 to 48 hpi), and later stages (48 to 168 hpi) of preimplantation development, and its impact upon the expression of five genes related to apoptosis (p53, bak, bcl-xL, p66Shc and caspase3), was assessed in resulting d 7 blastocysts, using real-time quantitative PCR. Total cell numbers, along with the number of apoptotic nuclei, as detected by the in situ cell death detection assay, were also calculated on d 7 in treated and non-treated control embryos. The results indicate that PFT-${\alpha}$, when administered at both early and later stages of porcine IVF embryo development, increases the incidence of apoptosis in resulting blastocysts. When administered at early cleavage stages, PFT-${\alpha}$ treatment was shown to reduce the developmental competence of porcine IVF embryos, as well as reducing the quality of resulting blastocysts in terms of overall cell numbers. In contrast, at later stages, PFT-${\alpha}$ administration resulted in marginally increased blastocyst development rates amongst treated embryos, but did not affect cell numbers. However, PFT-${\alpha}$ treatment induced apoptosis and apoptotic related gene expression, in all treated embryos, irrespective of the timing of treatment. Our results indicate that PFT-${\alpha}$ may severely compromise the developmental potential of porcine IVF embryos, and is a potent apoptotic agent when placed into porcine embryo culture media. Thus, caution should be exercised when using PFT-${\alpha}$ as a specific inhibitor of p53 mediated apoptosis, in the context of porcine IVF embryo culture systems.

A Literatural Investigation into lang Gyung - Ak's Theory of Myungmun (장경악(張景岳)의 명문학설(命門學說)에 관한 문헌적(文獻的) 고찰(考察))

  • Kim, Gyu-Yeol;Hong, Won-Sik
    • Journal of Korean Medical classics
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    • v.4
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    • pp.75-100
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    • 1990
  • As a result, the investigation into Gyung-Ak (景岳)'s theory of Myungmun (命門) was led to the next conclusions. First, Gyung-Ak (景岳) defmed Myungmun as the gate of Suncheon (先天) and Whoocheon (後天), by which the life of Suncheon is obtained and the life of Whoocheon is maintained. He maintained that Myungmun is located between two kindneys, not sided to the right as in the Nankyeong (難經), and considered the substance of Myungmun as Jagung (子宮 ${\fallingdotseq}$ uterus) or the other names as such Jaho (子戶), Jajang (子腸) Danjeon (丹田), Hyeolsil (血室), etc. On the essence or function of Myungmun it was considered as Taegeuk (太極) of the body which shapes the North Pole in the center of the body, and as the hinge of rise and fall, as controller of Soowha-action (水火作用) and Eumyang-changing (陰陽變化), and as storage of Suncheon Jinil-ki (先天 眞一之氣), the source of life and vitality and as the spring of Twelve-Jang (十二藏). Thus, the function of Five-Jang (五臟 ${\fallingdotseq}$ Five-Viscera) and Six-Boo (六腑 ${\fallingdotseq}$ Six-Bowels) and actions of life is obtainded by Myungmun, and the life and death of man and the change of life is related to that. Bi-Wi (脾胃 ${\fallingdotseq}$ Spleen & Stomach) as well as Myungmun is the root of Five-Jang and Six-Boo, but since Bi-Wi is the base of postnatal nutrition to belong to the son of Wonyang (元陽), Myungmun is treated more important as the mother of Bi-Wi. Sin (賢 ${fallingdotseq}$ Kidney) was perceived as inseparably related with Myungmun, but in the course of theoretical development the function of Sin was considered to be ultimately operated by the action of Myungmun. In the Theory of Jineum (眞陰論), Gyung-Ak full accounted the diverse nature of disease and patholog from Soowha-shortage of Myungmun, and presented the laws and methods of medical treatment to those. Finally, in his theory related to Myungmun, some logical contradiction and confusion in conceptions was discovered and the anatomy of Present age proved that the location of Jagung and DanJeon, which he recognized as the substance of Myungmun is not coincided. Summerizingly, the Gyung-Ak's theory of Myungmun closely related the theory of Myungmun to the theory of Eumyang-Jungki (陰陽精氣論), by whole discourse of the characteristics of physiology possessing Soowha of Myungmun on the foundation of Eumyang-hogeun (陰陽互根) and Jungki-hosaeng (精氣互生). Gyung-Ak regarded the function of Myungmun as more important than any other Jang, discoursed more systematically and more specifically about the Myungmun than any others, and presented the theory of Sin-Myung (賢命理論) and prescription which is important to Care of Health and Medical Treatment (養生治病), thus influenced very greatly on the development of Oriental Medicine.

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Potentiation of Anticancer Effect of Artesunate by Combination with Nonsteroidal Anti-inflammatory Drugs on Human Cancer Cells (Artesunate와 비스테로이드소염제 NSAID의 병용 처리에 의한 항암 활성 증강)

  • Moon, Hyun-Jung;Kang, Chi-Dug;Kim, Sun-Hee
    • Journal of Life Science
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    • v.31 no.10
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    • pp.873-884
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    • 2021
  • The purpose of present study is to investigate the role of artesunate (ART) in enhancing anticancer effect of nonsteroidal anti-inflammatory drug (NSAID) on human cancer cells, and we elucidate a possible molecular mechanism of this combination effect. We showed that the combined effect of ART with NSAID such as celecoxib (CCB) or dimethyl-CCB (DMC) in various type of human cancer cells. After ART treatment, the expression of p62, nuclear factor erythroid 2-like 2 (NRF2) and cancer stemness (CS)-related proteins including CD44, CD133, aldehyde dehydrogenase 1 (ALDH1), octamer-binding transcription factor 4 (Oct4), mutated p53 (mutp53) and c-Myc was down-regulated. ART induced autophagy as reduction of the autophagy receptor p62, which was associated with up-regulation of activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and simultaneous down-regulation of NRF2 and CS-related proteins was occurred in the human cancer cells. These results indicate a possibility that ART activates autophagy through ATF4-CHOP cascade leading to down-regulation of CS-related proteins and subsequently eradicated cancer stem cells. In addition, co-treatment with ART and imatinib was more effective than either drug alone on growth inhibition and apoptosis induction of cancer cells. In conclusion, induction of autophagy-dependent cell death by ART might play a critical role in mediating the synergistic effect of drug combination (ART/NSAID and ART/imatinib). Therefore, ART could be a promising candidate as a chemosensitizer to enhance the anticancer effects of NSAID and imatinib.

Gene Expression Profiling of 6-MP (6-mercaptopurine) in Liver

  • Kim Hyung-Lae;Kim Han-Na;Lee Eun-Ju
    • Genomics & Informatics
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    • v.4 no.1
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    • pp.16-22
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    • 2006
  • The KFDA (Korea Food & Drug Administration) has performed a collaborative toxicogenomics project since 2003. Its aim is to construct a toxicology database of 12 compounds administered to mice at initial phase. We chose 6-MP (6-mercaptopurine) which has been used in the treatment of childhood leukemia. It was administered at low (0.224 mg/kg) and at high (2.24 mg/kg) dose (5 mice per group) intraperitonealy to the postnatal 6 weeks mice, then the serum and liver were collected at the indicated time (6, 24 and 72 h) after scarification. Serum biochemical markers for liver toxicity were measured and histopathologic studies also were carried out. The gene expression profiling was carried out by using Applied Biosystems 1700 Full Genome Expression Mouse. By self-organization maps (SOM), we identified groups with unique gene expression patterns, some of them are supposed to be related to 6-MP induced toxicity, including lipid metabolism abnormality, inflammatory response, oxidative stress, ATP depletion and cell death. The potential toxic effects appearing as gene expression changes are dependent of the time of 6-MP but independent of the dosage of it. This study would contribute to establishment of international database as well as national one about hepatotoxicity.

Systemic Analysis on Laparoscope-Assisted Gastrectomy for Patients with Gastric Cancer

  • Hu, Jun-Hong;Tang, Hong-Na;Ma, Yong-Ping;Wang, Chen-Yu;Yao, Kun-Hou;Zhang, Jun-Jie;Ren, Xue-Qun
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.5
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    • pp.2027-2029
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    • 2015
  • Background: Laparoscope-assisted gastrectomy in treating patients with gastric cancers developed with a background of highly invasive traditional surgery and is being increasingly performed in the Asian Pacific area. This study systemically investigated the technique and clinical results for comparison with traditional radical subtotal gastrectomy for gastric cancers. Methods: Clinical studies evaluating the effectiveness and side effects of laparoscope-assisted gastrectomy in treating patients with gastric cancers were identified using a predefined search strategy. Summary rates of effectiveness and side effects of laparoscope-assisted gastrectomy were calculated. Results: Thirteen clinical studies which including 1,412 patients with gastric cancer treated by laparoscope-assisted gastrectomy were considered eligible for inclusion. Systemic analysis showed that, for all patients, the pooled resection rate was 100%. Major adverse effects were anastomotic stenosis, abdominal abscess, abdominal bleeding, postoperative ileus. Treatment related death occurred in 0. 71% (10/1412). Conclusion: This systemic analysis suggests that laparoscope-assisted gastrectomy in treating patients with gastric cancers is associated with good curative rate and acceptable complications.