• Title/Summary/Keyword: T98G cell

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Prophylactic and Therapeutic Potential of Asp f1 Epitopes in Naive and Sensitized BALB/c Mice

  • Chaudhary, Neelkamal;Mahajan, Lakshna;Madan, Taruna;Kumar, Anil;Raghava, Gajendra Pratap Singh;Katti, Seturam Bandacharya;Haq, Wahajul;Sarma, Puranam Usha
    • IMMUNE NETWORK
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    • v.9 no.5
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    • pp.179-191
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    • 2009
  • Background: The present study examines a hypothesis that short allergen-derived peptides may shift an Aspergillus fumigatus (Afu-) specific TH2 response towards a protective TH1. Five overlapping peptides (P1-P5) derived from Asp f1, a major allergen/antigen of Afu, were evaluated for prophylactic or therapeutic efficacy in BALB/c mice. Methods: To evaluate the prophylactic efficacy, peptides were intranasally administered to naive mice and challenged with Afu-allergens/antigens. For evaluation of therapeutic efficacy, the mice were sensitized with Afu-allergens/antigens followed by intranasal administration of peptides. The groups were compared for the levels of Afu-specific antibodies in sera and splenic cytokines evaluated by ELISA. Eosinophil peroxidase activity was examined in the lung cell suspensions and lung inflammation was assessed by histopathogy. Results: Peptides P1-, P2- and P3 decreased Afu-specific IgE (84.5~98.9%) and IgG antibodies (45.7~71.6%) in comparison with Afu-sensitized mice prophylactically. P1- and P2-treated ABPA mice showed decline in Afu-specific IgE (76.4~88%) and IgG antibodies (15~54%). Increased IgG2a/IgG1 and IFN-${\gamma}$/IL-4 ratios were observed. P1-P3 prophylactically and P1 therapeutically decreased IL-5 levels and eosinophil peroxidase activity. P1 decreased inflammatory cells' infiltration in lung tissue comparable to non-challenged control. Conclusion: Asp f1-derived peptide P1, prophylactically and therapeutically administered to Balb/c mice, is effective in regulating allergic response to allergens/antigens of Afu, and may be explored for immunotherapy of allergic aspergillosis in humans.

Physiological Activities and Inhibitory Effect of Extracts of Cynanchi wilfordii Radix and Perilla sikokiana against Cell Differentiation in 3T3-L1 Adipocytes (백하수오와 자소엽 추출물의 생리활성 및 3T3-L1 전지방세포에 대한 분화 억제 효과)

  • Kim, Seon Jeong;Kang, Seung Mi;Ko, Keon Hee;Nam, Sanghae
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.45 no.5
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    • pp.642-650
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    • 2016
  • Cynanchi wilfordii Radix (CW) and Perilla sikokiana (PS) were extracted under different conditions to study their antioxidant, anti-diabetic, and anti-obesity activities. Their potentials as functional food ingredients were investigated. The highest total phenol contents were $15.74{\pm}0.69mg/g$ for CW100 [100% fermented ethanol (FE) extract from CW] and $39.37{\pm}3.46mg/g$ for PS50 (50% FE extract from PS). When extracts were processed at 1 mg/mL, DPPH radical scavenging activities were $79.79{\pm}0.79%$ and $82.69{\pm}1.07%$, respectively, at CW100 and PS50. ABTS radical scavenging activities were $80.20{\pm}2.86%$ and $75.00{\pm}1.78%$, respectively, at CW100 and PS50. However, ferric reducing antioxidant power activities at 1 mg/mL were higher than 80% for PS under all extraction conditions. The highest ${\alpha}$-amylase inhibitory activities were $51.56{\pm}0.56{\sim}59.2{\pm}1.13%$ at CW50 and $46.70{\pm}0.32{\sim}66.17{\pm}0.55%$ at PS0. Cell differentiation inhibitory effects in 3T3-L1 adipocytes were $29.49{\pm}2.98%$ at CW100 and $23.31{\pm}0.61%$ at PS50. The inhibitory effect of the CW100-PS50 mixture was $43.03{\pm}1.63%$, which was significantly higher than those of individual extracts.

The role of protein arginine-methyltransferase 1 in gliomagenesis

  • Wang, Shan;Tan, Xiaochao;Yang, Bin;Yin, Bin;Yuan, Jiangang;Qiang, Boqin;Peng, Xiaozhong
    • BMB Reports
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    • v.45 no.8
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    • pp.470-475
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    • 2012
  • Protein arginine methyltransferase 1 (PRMT1), a type-I arginine methyltransferase, has been implicated in diverse cellular events. We have focused on the role of PRMT1 in gliomagenesis. In this study, we showed that PRMT1 expression was up-regulated in glioma tissues and cell lines compared with normal brain tissues. The knock-down of PRMT1 resulted in an arrest in the G1-S phase of the cell cycle, proliferation inhibition and apoptosis induction in four glioma cell lines (T98G, U87MG, U251, and A172). Moreover, an in vivo study confirmed that the tumor growth in nude mouse xenografts was significantly decreased in the RNAi-PRMT1 group. Additionally, we found that the level of the asymmetric dimethylated modification of H4R3, a substrate of PRMT1, was higher in glioma cells than in normal brain tissues and decreased after PRMT1 knock-down. Our data suggest a potential role for PRMT1 as a novel biomarker of and therapeutic target in gliomas.

Side Population Cell Level in Human Breast Cancer and Factors Related to Disease-free Survival

  • Jin, C.G.;Zou, T.N.;Li, J.;Chen, X.Q.;Liu, X.;Wang, Y.Y.;Wang, X.;Che, Y.H.;Wang, X.C.;Sriplung, Hutcha
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.3
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    • pp.991-996
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    • 2015
  • Side population (SP) cells have stem cell-like properties with a capacity for self-renewal and are resistant to chemotherapy and radiotherapy. Therefore the presence of SP cells in human breast cancer probably has prognostic value. Objective: To investigate the characteristics of SP cells and identify the relationship between the SP cells levels and clinico-pathological parameters of the breast tumor and disease-free survival (DFS) in breast cancer patients. Materials and Methods: A total of 122 eligible breast cancer patients were consecutively recruited from January 1, 2006 to December 31, 2007 at Yunnan Tumor Hospital. All eligible subjects received conventional treatment and were followed up for seven years. Predictors of recurrence and/or metastasis and DFS were analyzed using Cox regression analysis. Human breast cancer cells were also obtained from fresh human breast cancer tissue and cultured by the nucleic acid dye Hoechst33342 with Verapami. Flow cytometry (FCM) was employed to isolate the cells of SP and non-SP types. Results: In this study, SP cells were identified using flow cytometric analysis with Hoechst 33342 dye efflux. Adjusted for age, tumor size, lymph nodal status, histological grade, the Cox model showed a higher risk of recurrence and/or metastasis positively associated with the SP cell level (1.75, 1.02-2.98), as well as with axillary lymph node metastasis (2.99, 1.76-5.09), pathology invasiveness type (1.7, 1.14-2.55), and tumor volume doubling time (TVDT) (1.54, 1.01-2.36). Conclusions: The SP cell level is independently associated with tumor progression and clinical outcome after controlling for other pathological factors. The axillary lymph node status, TVDT and the status of non-invasive or invasive tumor independently predict the prognosis of breast cancer.

Effects of Rumen Protected Choline on In vitro Ruminal Fermentation and Milk Production and Its Composition in Lactating Cows (반추위 보호 Choline이 In vitro 반추위 발효특성과 착유우의 유생산 및 유조성분에 미치는 영향)

  • Park, Byung-Ki;Kim, Byong-Wan;Jang, Hyun-Yong;Shin, Jong-Suh
    • Journal of The Korean Society of Grassland and Forage Science
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    • v.28 no.3
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    • pp.255-264
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    • 2008
  • This study was conducted to evaluate the effects of rumen protected choline on in vitro ruminal fermentation and milk production and its composition in Holstein cows. Experiments were done with three treatment groups, basal diet without any supplement (T1), basal diet+23g/d of mixture of choline and wheat shorts (T2) and basal diet + 25.56 g/d of rumen protected choline (T3). The in vitro ruminal pH and ammonia concentrations were similar for three treatments during all incubation periods except for the in vitro ruminal pH on 3 hr incubation and ammonia concentrations on 9 hr incubation. No significant difference was found in the concentrations of acetate and total-VFA. The propionate and butyrate concentrations were not affected by the rumen protected choline except on 6 hr incubation on which the propionate and butyrate concentrations were intermediate (8.98 mg/dl) and least (3.22 mg/dl), respectively. Higher milk yield and milk fat and lactose were resulted in the rumen protected choline. However, the rumen protected choline did not affect the milk protein, solids not fat, total solids, MUN, somatic cell count. It is concluded that the rumen protected choline can be effective materials to improve the milk production, milk fat and lactose without little change on in vitro ruminal fermentation.

Evaluation of Antioxidant, Anti-Inflammatory, Antithrombotic, and Antiobesity Activities in Cultured Edible Plants to Increase Farm Income (농가소득 창출을 위한 식용식물의 항산화, 항염, 항혈전 및 항비만 효과 탐색)

  • Lee, Seon-Hye;Kim, Nam-Seok;Choi, Bong-Kyoum;Park, Yeon-Hee;Kim, Jung-Bong;Jang, Hwan-Hee;Hwang, Yu-Jin;Choe, Jeong-Sook;Lee, Sung-Hyen
    • The Korean Journal of Community Living Science
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    • v.28 no.1
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    • pp.29-43
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    • 2017
  • We studied the antioxidant, the anti-inflammatory, antithrombotic, and antiobesity activities of seven different kinds of edible plants. 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ABTS radical scavenging activities were determined as a measurement of antioxidant activity. NO production inhibition by the macrophage cell line (Raw 264.7) treated with lipopolysaccharide (LPS) was carried out to assess anti-inflammatory activity. Thrombin inhibitory activity was measured for its antithrombotic function and inhibition of 3T3-L1 cell differentiation was evaluated as a measurement of antiobesity activity. Total phenolic components and total flavonoid contents were measured to determine functional materials in medicinal plants. Common sage, Japanese lady bell, and hairy agrimony showed high antioxidant activity ($IC_{50}$) of less than $100{\mu}g/mL$. All samples used in this study showed anti-inflammatory activity. Common sage, hairy agrimony, and hooker chives showed antithrombotic effects. Hairy agrimony showed the highest antithrombotic effect (98.1%). Common sage, Japanese lady belly, hairy agrimony, and hooker chives showed reduced 3T3-L1 cell differentiation and hooker chives strongly inhibited lipid accumulation in the cells compared to other medicinal plants. Common sage and hairy agrimony contained more than 1 mg GAE/g of phenolic compounds and more than 1 mg CE/g of flavonoids. Functional activities were different by plant part and extraction method from each sample. These results suggest that common sage, Japanese lady belly, hairy agrimony, and hooker chives may be used as healthy food sources with antioxidant, anti-inflammatory, antithrombotic, and antiobesity activities, and appropriate extracting methods from each plant need to be developed.

Impact of Postoperative Oral Administration of UFT for Completely Resected pT2N0 Non-Small Cell Lung Cancer (완전 절제된 비소세포폐암 병기 IB (pT2N0) 환자에서 수술 후 UFT의 효과)

  • Lee, Jin-Gu;Park, In-Kyu;Kim, Dae-Joon;Kim, Kil-Dong;Cho, Sang-Ho;Chung, Kyung-Young
    • Journal of Chest Surgery
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    • v.40 no.6 s.275
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    • pp.428-434
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    • 2007
  • Background: Recent studies have suggested that UFT may be an effective adjuvant therapy for completely resected IB (pT2N0) non-small cell lung cancer (NSCLC). We designed this study to clarify the feasibility of performing adjuvant chemotherapy with UFT for completely resected IB nor-small cell lung cancer, Material and Method: We randomly assigned patients suffering with completely resected IB non-small cell lung cancer to receive either UFT 3g for 2 year or they received no treatment. All patients had to be followed until death or the cut-off date (December 31 2006). Result: From June 2002 through December 2004, 64 patients were enrolled. Thirty five patients were assigned to receive UFT (the UFT group) and 29 patients were assigned to observation (the control group). A follow-up surrey on the 3 year survival rate was successfully completed for all the patients. The median follow-up time for all the patients was 32.8 months. In the UFT group, the median time of administration was 98 weeks (range: $2{\sim}129$ weeks). The rate of compliance was 88.2% at 6 months, 87.5% at 12 months, 80.6% at 18 month and 66.7% at 24 months. Seven recurrences (24.1%) occurred in the control group and six (17.1%) occurred in the UFT group (p=0,489). The three-year disease free survival rate was 71.3% for the control group and 82.0% for the UFT group (p=0.331). On the subgroup analysis, the three-year disease free survival rate for the patients with adenocacinoma was 45.0% for the control group and 75.2% for the UFT group (p=0.121). The three-year disease free survival rate for the patients with non-adenocarcinoma was 88.1% for the control group and 88.9% for the UFT group (p=0.964), Conclusion: Postoperative oral administration of UFT was well-tolerated. Adjuvant chemotherapy with UFT for completely resected pT2N0 adenocarcinoma of the lung could be expected to improve the disease free survival, but this failed to achieve statistical significance. A prospective randomized study for a large number of patients will be necessary.

A Novel Suberoylanilide Hydroxamic Acid Histone Deacetylase Inhibitor Derivative, N25, Exhibiting Improved Antitumor Activity in both Human U251 and H460 Cells

  • Zhang, Song;Huang, Wei-Bin;Wu, Li;Wang, Lai-You;Ye, Lian-Bao;Feng, Bing-Hong
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.10
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    • pp.4331-4338
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    • 2014
  • $N^1$-(2, 5-dimethoxyphenyl)-$N^8$-hydroxyoctanediamide (N25) is a novel SAHA cap derivative of HDACi, with a patent (No. CN 103159646). This invention is a hydroxamic acid compound with a structural formula of $RNHCO(CH_2)6CONHOH$ (wherein R=2, 5dimethoxyaniline), a pharmaceutically acceptable salt which is soluble. In the present study, we investigated the effects of N25 with regard to drug distribution and molecular docking, and anti-proliferation, apoptosis, cell cycling, and $LD_{50}$. First, we designed a molecular approach for modeling selected SAHA derivatives based on available structural information regarding human HDAC8 in complex with SAHA (PDB code 1T69). N25 was found to be stabilized by direct interaction with the HDAC8. Anti-proliferative activity was observed in human glioma U251, U87, T98G cells and human lung cancer H460, A549, H1299 cells at moderate concentrations ($0.5-30{\mu}M$). Compared with SAHA, N25 displayed an increased antitumor activity in U251 and H460 cells. We further analyzed cell death mechanisms activated by N25 in U251 and H460 cells. N25 significantly increased acetylation of Histone 3 and inhibited HDAC4. On RT-PCR analysis, N25 increased the mRNA levels of p21, however, decreased the levels of p53. These resulted in promotion of apoptosis, inducing G0/G1 arrest in U251 cells and G2/M arrest in H460 cells in a time-dependent and dose-dependent manner. In addition, N25 was able to distribute to brain tissue through the blood-brain barrier of mice ($LD_{50}$: 240.840mg/kg). In conclusion, our findings demonstrate that N25 will provide an invaluable tool to investigate the molecular mechanism with potential chemotherapeutic value in several malignancies, especially human glioma.

Immuno-modulatory and Antitumor Effect of Crude Polysaccharides Extracted from Sclerotium of Grifola umbellata (저령(Grifola umbellata)의 균핵에서 추출한 조다당류의 면역활성 및 항암 효과)

  • Oh, Yun-Hee;Lee, U-Youn;Lee, Min-Woong;Shim, Mi-Ja;Lee, Tae-Soo
    • The Korean Journal of Mycology
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    • v.32 no.1
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    • pp.23-30
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    • 2004
  • Neutral salt-soluble, hot water-soluble and methanol-soluble materials (hereinafter referred to Fr. NaCl, Fr. HW and Fr. MeOH, respectively) were extracted from sclerotium of Grifola umbellata. The Fr. NaCl and Fr. HW did not show any direct cytotoxicity against NIH3T3, Sarcoma 180 and MCF-7, but Fr. MeOH showed cytotoxicity against these cell lines at the concentration of $1,000\;{\mu}g/ml$. Intraperitoneal injection with Fr. NaCl showed antitumor effect with life prolongation of 66.7% and decrease the number of Sarcoma 180 cells of 54.2% in mice inoculated with Sarcoma 180. Fr. NaCl improved the immunopotentiation activity through alternative complement pathway and the alkaline phosphatase activity by $85.05{\sim}88.73%$ and 6 folds, respectively. The number of peritoneal exudate cells and the circulating leucocytes were increased by 1.7 and 3.6 folds in the Fr. NaCl treating group compared with the control group, respectively. The weight of immunoorgans such as liver, spleen and thymus were also gradually increased. The hematological analysis of the Fr. NaCl group was similar with that of the control group. The total polysaccharide and protein contents of Fr. NaCl were 98.25% and 1.44%, respectively. These results indicate that the antitumor activity of Fr. NaCl was exerted through immunopotentiation, but not through cytotoxicity against the tumor cells.

Protection of UV-derived Skin Cell Damage and Anti-irritation Effect of Juniperus chinensis Xylem Extract (향나무추출물의 광손상으로부터 피부세포 보호와 자극완화 효과에 대한 연구)

  • 김진화;박성민;심관섭;이범천;표형배
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.30 no.1
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    • pp.63-71
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    • 2004
  • The human skin is constantly exposed to environmental irritants such as ultraviolet, smoke, chemicals. Free radicals and reactive oxygen species (ROS) caused by these environmental facts play critical roles in cellular damage. These irritants are in themselves damaging to the skin structure but they also participate the immensely complex inflammatory reaction. The purpose of this study was to investigate the skin cell protective effect of Juniperus chinensis xylem extract on the UV and SLS-induced skin cell damages. We tested free radical and superoxide scavenging effect in vitro. We found that Juniperus chinensis xylem extracts had potent radical scavenging effect by 98% at 100 $\mu\textrm{g}$/mL. Fluorometric assays of the proteolytic activities of matrix metalloproteinase-l(MMP-1, collagenase) were performed using fluorescent collagen substrates. UV A induced MMP-1 synthesis and activity were analyzed by enzyme-linked immunosorbent assay (ELISA) and gelatin-based zymography in skin fibroblasts. The extract of Juniperus chinensis showed strong inhibitory effect on MMP-1 activities by 97% at 100 $\mu\textrm{g}$/mL and suppressed the UVA induced expression of MMP-1 by 79% at 25 $\mu\textrm{g}$/mL. This extract also showed strong inhibition on MMP-2 activity in UVA irradiated fibroblast by zymography. We also examined anti-inflammatory effects by the determination test of proinflammatory cytokine, interleukin 6 in HaCaT keratinocytes. In this test Juniperus chinensis decreased expression of interleukin 6 about 30%. Expression of prostaglandin E$_2$, (PGE$_2$) after UVB irradiation was measured by competitive enzyme immunoassay (EIA) using PGE$_2$ monoclonal antibody. At the concentrations of 5-50 $\mu\textrm{g}$/mL of the extracts, the production of PGE$_2$ by HaCaT keratinocytes (24 hours after 10 mJ/$\textrm{cm}^2$ UVB irradiation) was significantly inhibited in culture supernatants (p〈0.05). The viability of cultured HaCaT keratinocytes was significantly reduced at the doses of above 10 mJ/$\textrm{cm}^2$ of UVB irradiation, but the presence of these extracts improved cell viability comparing to control after UVB irradiation. We also investigated the protective effect of this extract in sodium lauryl sulfate (SLS)-induced irritant skin reactions from 24 hour exposure. Twice a day application of the extract for reducing local inflammation in human skin was done. Irritant reactions were assessed by various aspects of skin condition, that is, erythema (skin color reflectance) and transepidermal water loss (TEWL). After 5 days the extract was found to reduce SLS-induced skin erythema and improve barrier regeneration when compared to untreated symmetrical test site. In conclusion, our results suggest that Juniperus chinensis can be effectively used for the prevention of UV and SLS-induced adverse skin reactions such as radical production, inflammation and skin cell damage.