• Title/Summary/Keyword: SURVIVAL

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Apoptotic Effects and Cell Cycle Arrest Effects of Extracts from Cnidium monnieri (L.) Cusson through Regulating Akt/mTOR/GSK-3β Signaling Pathways in HCT116 Colon Cancer Cells (HCT116 대장암세포에서 AKT/mTOR/GSK-3β 신호경로 조절을 통한 벌 사상자 추출물(CME)의 apoptosis 및 cell cycle arrest 효과)

  • Lim, Eun Gyeong;Kim, Guen Tae;Kim, Bo Min;Kim, Eun Ji;Ha, Sung Ho;Kim, Sang-Yong;Kim, Young Min
    • Journal of Life Science
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    • v.26 no.6
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    • pp.663-672
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    • 2016
  • The Cnidium monnieri (L.) Cusson is an annual plant distributed in China and Korea. The fruit of C. monnieri is used as a medicinal herb that is effective for the treatment of carbuncle and pain in female genitalia. However, the anti-cancer effects of CME have not yet been reported. In this study, we assessed the apoptotic effects and cell cycle arrest effects of ethanol extracts from C. monnieri on HCT116 colon cancer cells. The results of an MTT assay and LDH assay demonstrated a decrease in cell viability and the cytotoxic effects of CME. In addition, the number of apoptotic body and the apoptotic rate were increased in a dose-dependent manner through Hoechst 33342 staining and Annexin V-PI double staining. In addition, cell cycle arrest occurred at the G1 phase by CME. Protein kinase B (Akt) plays an important role in cancer cell survival, growth, and division. Akt down-regulates apoptosis-mediated proteins, such as mammalian target of rapamycin (mTOR), p53, and Glycogen Synthase kinase-3β (GSK-3β). CME could regulate the expression levels of p-Akt, p-mTOR, p-GSK-3β, Bcl-2 family members, caspase-3, and PARP. Furthermore, treatment with CME, LY294002 (PI3K/Akt inhibitor), BIO (GSK-3β inhibitor), and Rapamycin (mTOR inhibitor) showed that apoptotic effects occurred through the regulation of the AKT/mTOR/GSK-3β signaling pathway. Our results demonstrated CME could induce apoptosis and cell cycle arrest in HCT116 colon cancer cells.

The Extract from Artemisia annua Linné. Induces p53-independent Apoptosis through Mitochondrial Signaling Pathway in A549 Lung Cancer Cells (A549 폐암세포에서 미토콘드리아 경로를 통한 개똥쑥 추출물의 apoptosis 유도 효과)

  • Kim, Bo-Min;Kim, Guen-Tae;Kim, Eun-Ji;Lim, Eun-Gyeong;Kim, Sang-Yong;Kim, Young-Min
    • Journal of Life Science
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    • v.26 no.8
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    • pp.887-894
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    • 2016
  • The extract from Artemisia annuain L.(AAE) is known as a medicinal herb that is effective against cancer. Apoptosis is the process of programmed cell death, and mitochondria are known to play a central role in cell death control. In this study, we evaluated the p53-independent apoptosis of extract of AAE through downregulation of Bcl-2 and the mitochondrial pathway in A549 (lung cancer cells). AAE may exert cancer cell apoptosis through regulating p-Akt, Cox-2, p53 and mitochondria-mediated apoptotic proteins. p-Akt/cox-2 is known to play an important role in cell proliferation and cell survival. The Bcl-2 pro-apoptotic proteins (such as Bax, Bak and Bim) mediate the permeabilization of the mitochondrial outer membrane. Treatment of AAE reduces p-Akt, p-Mdm2, cox-2 and anti-apoptotic proteins (such as Bcl-2), while tumor suppressor p53 and pro-apoptotic proteins. Activation of Bax/Bak releases cytochrome c from mitochondria to the cytosol to activate a caspase. Caspase-3 is the major effector caspase associated with apoptotic pathways. Caspase-3 generally exists in cytoplasm in the form of a pro-enzyme. In the initiation stage of apoptosis, caspase-3 is activated by proteolytic cleavage and activated caspase-3 cleaves poly (ADP-ribose) polymerase (PARP). We treated Pifithrin-α (p53 inhibitor) and Celecoxib (Cox-2 inhibitor) to learn the relationship between the signal transduction of proteins associated with apoptosis. These results suggest that AAE induces apoptosis through a p53-independent pathway in A549.

LP-M, a Novel Butanol-Extracts Isolated from Liriope platyphylla, could Induce the Neuronal Cell Survival and Neuritic Outgrowth in Hippocampus of Mice through Akt/ERK Activation on NGF Signal Pathway (맥문동(Liriope platyphylla)의 새로운 부탄올 추출물인 LP-M이 Akt/ERK NGF receptor signaling pathway를 통해 뇌조직에서 신경세포의 생존과 성장에 미치는 영향에 관한 연구)

  • Nam, So-He;Choi, Sun-Il;Goo, Jun-Seo;Kim, Ji-Eun;Lee, Yoen-Kyung;Hwang, In-Sik;Lee, Hye-Ryun;Lee, Young-Ju;Lee, Hong-Gu;Choi, Young-Whan;Hwang, Dae-Youn
    • Journal of Life Science
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    • v.21 no.9
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    • pp.1234-1243
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    • 2011
  • Liriope platyphylla has been used in oriental medicine as an effective medical plant to improve symptoms of cough, sputum production, neurodegenerative disorders, obesity and diabetes for long time. In order to investigate the effects of novel extracts on nerve growth factors (NGF)-stimulated neuritic outgrowth, the alteration of NGF expression and NGF receptor signaling pathway were detected in neuroblastoma cells and C57BL/6 mice. Of a total of 13 novel extracts, 4 extracts (LP-E, LP-M, LP-M50, LP2E17PJ) showed high viability on MTT assay. Also, all of these extracts induced NGF secretion and NGF mRNA expression in neuroblastoma cells. However, the NGF-induced neuritic outgrowth from PC12 cells was only stimulated by LP-E, LP-M and LP-M50. Furthermore, we selected LP-M as a best candidate, based on method and amounts of extraction, in order to verify its effect in mice. C57BL/6 mice were treated with 50 mg/kg of LP-M for 2 weeks and the effects on NGF regulation were analyzed with various methods. The expression of NGF mRNA was significantly increased in LP-M treated mice compared to vehicle treated mice. Also, the signaling pathway of p75NTR was inhibited in the cortex by LP-M treatment, with no change in the hippocampus of brain. However, the signaling pathway of TrkA was dramatically activated in only hippocampus via LP-M treatment. Therefore, these results suggest that the novel four extracts of L. platyphylla may contribute to the regulation of NGF expression and secretion in neuronal cells. LP-M was especially considered to be an excellent candidate for a neurodegenerative disease-therapeutic drug.

Effects of Covering Materials on Prevention of Freeze Damage and Labor Saving in Saururus chinensis Baill During Wintering (삼백초의 월동 피복재 종류별 동해방지 및 노동력 절감효과)

  • Nam, Sang-Young;Kim, In-Jae;Kim, Min-Ja;Yun, Tae;Lee, Cheol-Hee;Park, Sung-Gue;Lee, Woo-Young;Kim, Hong-Sig
    • Korean Journal of Medicinal Crop Science
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    • v.13 no.6
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    • pp.287-292
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    • 2005
  • To investigate the effects of heat conservation materials on freeze damage and weed occurrence during overwintering in Saururus chinensis, Temperature difference was $6.9^{\circ}C$ in chaff, and was lower than those ranged from 9.7 to $14.4^{\circ}C$ in other materials. Heat conservation index, calculated from average temperatures below $-10^{\circ}C$ of earth's surface during the winter, was higher $1.7^{\circ}C\;and\;1.5^{\circ}C$ in chaff and lagging, respectively than in straw. Preservation of water is greater $9.6{\sim}26.1%$ in covering than in open field, and it increased in the order of lagging > chaff > straw among heat conservation materials. The survival rate of rhizome was increased in the order of 99% in lagging > 75% in chaff > 58% in straw, 32% in open field after overwintering, budbreak began fast, and the numbers of total budbreak per unit area were greater 22 times in lagging than 35.0 units in open field. Weeds occurrence was decreased in covering, i.e., $12.0{\sim}33.2\;units/m^2,\;7.3{\sim}10.7\;kg/10a$ of dry weight, and $5.6{\sim}6.4\;hours/10a$ of labor input compared with $157.2\;units/m^2,\;28.9\;kg/10a$ of dry weight, and 65.7 hours/10a of labor input in open field. Growth of top part was better in covering than in open field, and the number of tillers per unit area showed $347{\sim}396$ compared with 293 in open field. Marketable yields of dried stem and leaves and rhizome were higher $69{\sim}87%\;and\;58{\sim}88%$, respectively in covering than in open field, and among heat conservation materials, those were highest in lagging.

Variations in Mutant Plants by chemical mutagen treatments of Dianthus superbus L. (술패랭이에서 화학돌연변이물질 처리에 따른 돌연변이 유기 및 변이 분석)

  • Lee, Kwang-Hoe;Lim, Jung-Dae;Yu, Chang-Yeon
    • Korean Journal of Medicinal Crop Science
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    • v.8 no.4
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    • pp.334-341
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    • 2000
  • This study was conducted to determine the effects and optimum concentrantion of chemical mutagens, colchicine, EMS (ethyl methan sulfonate), MNU (1-methyl-3-1­-nitrosoguanidinenitro), sodium azide $(NaN_3)$ for induction of mutant plants. In order to induce the mutants of Dianthus superbus L, immature seed were pre-soaked in the warter adding each mutagens and concentration of EMS, colchicine, MNU, and sodium azide $(NaN_3)$. Comparision of morphological characteristic and seed germination in each mutant plants differed depending on mutagen sources and their concentrations. When 0.2% EMS were treated on seed, germination decreased to 12% while untreated control was germinated 76.6% for twenty days. Treatments of colchicine appeared higher germination than other mutagen but not survived. The survival rate was extremely decreased in MNU treatment at 0.5mM and chlorophyll-mutant plantlets were obtained by sodium azide treatment at 0.2mM. Chlorophyll mutants were produced by pre-soaking the immature seed of Dianthus superbus L. with mutagen, sodium azide. The control plants appeared normal green leaf color, while mutant plant after mutagenic treatment of immature seed results in yellow­-green stripes and albino in normal green leaf tissue. RAPD was carried out to check the genetic modification of regenerated plants by mutagen treatments at 0.2mM sodium azide. Three polymorphic DNA fragments out of thirty-seven obtained by RAPDs were observed in regenerated plants using five decamer primers.

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Factors Predicting the Development of Radiation Pneumonitis in the Patients Receiving Radiation Therapy for Lung Cancer (방사선 치료를 시행 받은 폐암 환자에서 방사선 폐렴의 발생에 관한 예측 인자)

  • An, Jin Yong;Lee, Yun Sun;Kwon, Sun Jung;Park, Hee Sun;Jung, Sung Soo;Kim, Jin whan;Kim, Ju Ock;Jo, Moon Jun;Kim, Sun Young
    • Tuberculosis and Respiratory Diseases
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    • v.56 no.1
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    • pp.40-50
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    • 2004
  • Background : Radiation pneumonitis(RP) is the major serious complication of thoracic irradiation treatment. In this study, we attempted to retrospectively evaluate the long-term prognosis of patients who experienced acute RP and to identify factor that might allow prediction of RP. Methods : Of the 114 lung cancer patients who underwent thoracic radiotherapy between December 2000 and December 2002, We performed analysis using a database of 90 patients who were capable of being evaluated. Results : Of the 44 patients(48.9%) who experienced clinical RP in this study, the RP was mild in 33(36.6%) and severe in 11(12.3%). All of severe RP were treated with corticosteroids. The median starting corticosteroids dose was 34 mg(30~40) and median treatment duration was 68 days(8~97). The median survival time of the 11 patients who experienced severe RP was significantly poorer than the mild RP group. (p=0.046) The higher total radiation dose(${\geq}60Gy$) was significantly associated with developing in RP.(p=0.001) The incidence of RP did not correlate with any of the ECOG performance, pulmonary function test, age, cell type, history of smoking, radiotherapy combined with chemotherapy, once-daily radiotherapy dose fraction. Also, serum albumin level, uric acid level at onset of RP did not influence the risk of severe RP in our study. Conclusion : Only the higher total radiation dose(${\geq}60Gy$) was a significant risk factor predictive of RP. Also severe RP was an adverse prognostic factor.

Treatment Outcomes and Prognostic Factors in Patients with Multidrug-Resistant Tuberculosis in Korean Private Hospitals (국내 민간병원에서 치료한 다제내성결핵 환자의 치료 결과 및 예후 인자)

  • Park, Jin-Kyeong;Koh, Won-Jung;Kim, Deog-Kyeom;Kim, Eun-Kyung;Kim, Yu-Il;Kim, Hee-Jin;Kim, Tae-Hyung;Kim, Jae-Yeol;Park, Moo-Suk;Park, I-Nae;Park, Jae-Seuk;Lee, Ki-Man;Song, Sook-Hee;Lee, Jin-Hwa;Lee, Seung-Heon;Lee, Hyuk-Pyo;Yim, Jae-Joon;Lim, Jae-Min;JeGal, Yang-Jin;Jung, Ki-Hwan;Huh, Jin-Won;Choi, Jae-Chol;Shim, Tae-Sun
    • Tuberculosis and Respiratory Diseases
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    • v.69 no.2
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    • pp.95-102
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    • 2010
  • Background: The increasing rate of drug-resistant tuberculosis (TB) is a threat to the public health and TB control. In Korea, about 75~80% of TB patients are treated in private hospitals and the rate has been continuously increasing since 2000. Methods: On a retrospective basis, we enrolled 170 newly diagnosed with or retreated for multidrug-resistant TB (MDR-TB) in 2004 from 21 private hospitals. We extracted the following demographics and treatment history from patient medical records: initial treatment outcomes, cumulative survival rates, treatment outcomes, and prognostic factors. Results: Of the 170 patients, the majority were male (64.1%), the mean age was 44.5 years old, and mean body-mass-index was $20.2kg/m^2$. None of the patients tested positive for HIV. Eleven (6.5%) were confirmed to have extensively drug-resistant TB (XDR-TB) at treatment initiation. Treatment success rates were not different between XDR-TB (36.4%, 4/11) and non-XDR MDR-TB (51.6%, 82/159). Default rate was high, 21.8% (37/170). Far advanced disease on X-ray was a significant negative predictor of treatment success; advanced disease and low BMI were risk factors for all-cause mortality. Conclusion: In private hospitals in Korea, the proportion of XDR-TB in MDR-TB was comparable to previous data. The treatment success rate of MDR-/XDR-TB remains poor and the failure rate was quite high. Adequate TB control policies should be strengthened to prevent the further development and spread of MDR-/XDR-TB in Korea.

Early Responses of Planted Quercus serrata Seedlings and Understory Vegetation to Artificial Gap Treatments in Black Locust Plantation (아까시나무림에서 인공 숲틈 처리에 대한 졸참나무 식재목 및 하층식생의 초기 반응)

  • Cho, Yong-Chan;Kim, Jun-Soo;Lee, Jung-Hyo;Lee, Heon-Ho;Ma, Ho-Seob;Lee, Chang-Seok;Cho, Hyun-Je;Bae, Kwan-Ho
    • Journal of Korean Society of Forest Science
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    • v.98 no.1
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    • pp.94-105
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    • 2009
  • Black locust (Robinia pseudoacacia) stand is representative lowland exotic plantation with low ecological quality and arrested succession in South Korea. To facilitate succession and restore natural vegetation, small canopy gaps (${\sim}57m^2$), which can modify minimally structural variables and reduce restoration related disturbances on stand, was established in the black locust stand, and oak (Quercus serrata) seedlings were introduced in the gap. Two types of varying levels were introduced for gap creation; cutting (C) and girdling (G) on canopies. Understory removal (CU and GU) treatment was applied as subtypes of structural modification. Growth (diameter, height and leaf area) of target species and responses (species composition, diversity and coverage) of understory community were monitored during study years (2007~2008). Canopy openness was different significantly among treatments but not for light availability. Based on the result of logistic regression, growth of height and leaf area of seedlings were significant variables on seedling survival. Height and leaf area of seedlings were increased during study years, although radial growth was reduced. During study years, there were no significant differences in species composition and diversity, and total coverage increased about 20%. Increase of resources by gap creation and understory removal likely affect growth of target species. Small gap creation was effective to reduce understory responses in composition and diverstiy. Synthesized, growth of target species and responses of understory community to small canopy gap creation exhibited, in short term, possibility of utilization in alternative forest restoration and management option. Long-term monitoring is necessary to certificate effect of artificial gap creation on forest restoration.

Anti-Stress Effect of Punica granatum L. Extract against Sleep Deprivation-Induced Impairment (석류 열수 추출물의 수면박탈을 유도한 Rat 모델에서의 항스트레스 효과)

  • Na, Ju-Ryun;Kim, Sunoh;Jo, Ara;Bae, Donghyuck;Oh, Kyo-Nyeo;Kim, Yong Jae;Lee, Yoo-Hyun;Jun, Woojin
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.11
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    • pp.1533-1543
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    • 2016
  • The anti-stress effects of Punica granatum L. (family Lythraceae, PG) on $H_2O_2$/corticosterone (CORT)-induced stress in cells and sleep-deprived rats were investigated. The PG extract showed neuroprotective effects in SH-SY5Y cells against $H_2O_2$/CORT-induced stress. Sleep deprivation led to behavioral, hormonal, and biochemical alterations in the animal model. The effects of P. granatum on physiological, behavioral, and biochemical parameters aggravated by sleep deprivation were investigated. Sleep deprivation impaired physiological (survival, body weight, and drowsiness scores) and behavioral (rotarod, passive avoidance, hot hyperalgesia, and Y maze) parameters as well as biochemical factors (cortisol, serotonin, dopamine, testosterone, and growth factor I contents in serum). These parameters were significantly recovered by PG extract in a concentration-dependent manner. The PG extract also enhanced catalase, superoxide dismutase, and non-enzymatic antioxidative activities such as glutathione compared to sleep-deprived rats. On the basis of these results, our findings suggest that Punica granatum prevents impairment of body functions induced by sleep deprivation and related oxidative damage.

p53 Gene Mutation in Gastric Cancer Tissue (위암조직에서 p53 유전자의 돌연변이)

  • Ku, Ki-Beom;Park, Seong-Hoon;Cheong, Ho-Young;Lee, Myung-Hoon;Yu, Wan-Sik
    • Journal of Gastric Cancer
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    • v.6 no.4
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    • pp.214-220
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    • 2006
  • Purpose: p53 is one of the most commonly mutated genes in human tumors. The aim of this study was to analyze p53 mutation in gastric cancer and its correlations with the clinicopathologic variables to clarify the usefulness of p53 mutation as a prognostic factor. Materials and Methods: Specimens from 331 patients with gastric cancer who underwent a gastrectomy between March 1999 and April 2001 at the Kyungpook National University Hospital were used. p53 gene mutations were assessed by using a polymerase chain-reaction single-strand conformation polymorphism (PCR-SSCP) analysis. The correlations between p53 gene mutation and clinocopathologic parameters were analyzed. Results: p53 mutations were found in 66 (19.9%) tumors. Among those 66 cases, mutations were seen in 23 tumors at axon 5, in 8 at exon 6, in 21 at exon 7, and in 17 at exon 8. Two mutations were shown in 3 tumors. Thiriy-six (23.1%) of 156 intestinal-type tumors and 19 (13.1%) of 145 diffuse-type tumors showed p53 gene mutation (P=0.007). The frequency of p53 gene mutation didn't show any significant differences according to age, sex, stage, location, or gross type. Exon 5 mutations showed more frequently in intestinal-type tumors than in diffuse-type tumors (9.7% vs. 2.8%, P=0.024), and p53 mutation were more frequent in lymph nodes metastasis group than lymph nodes non-metastasis group with statistical significance (25.0% vs 15.6%, P=0.034). The five-year survival rate showed no statistically significant difference with p53 mutation (P=0.704). Conclusion: p53 mutations assessed by PCR-SSCP had little value as a prognostic factor after gastrectomy in patients with gastric cancer.

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