• Title/Summary/Keyword: Phase II study

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Dietary Aloe Vera Gel Powder and Extract Inhibit Azoxymethane-induced Colorectal Aberrant Crypt Foci in Mice Fed a High-fat Diet

  • Chihara, Takeshi;Shimpo, Kan;Kaneko, Takaaki;Beppu, Hidehiko;Higashiguchi, Takashi;Sonoda, Shigeru;Tanaka, Miyuki;Yamada, Muneo;Abe, Fumiaki
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.2
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    • pp.683-687
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    • 2015
  • Aloe vera gel exhibits protective effects against insulin resistance as well as lipid-lowering and anti-diabetic effects. The anti-diabetic compounds in this gel were identified as Aloe-sterols. Aloe vera gel extract (AVGE) containing Aloe-sterols has recently been produced using a new procedure. We previously reported that AVGE reduced large-sized intestinal polyps in Apc-deficient Min mice fed a high fat diet (HFD), suggesting that Aloe vera gel may protect against colorectal cancer. In the present study, we examined the effects of Aloe vera gel powder (AVGP) and AVGE on azoxymethane-induced colorectal preneoplastic aberrant crypt foci (ACF) in mice fed a HFD. Male C57BL/6J mice were given a normal diet (ND), HFD, HFD containing 0.5% carboxymethyl cellulose solution, which was used as a solvent for AVGE (HFDC), HFD containing 3% or 1% AVGP, and HFDC containing 0.0125% (H-) or 0.00375% (L-) AVGE. The number of ACF was significantly lower in mice given 3% AVGP and H-AVGE than in those given HFD or HFDC alone. Moreover, 3% AVGP, H-AVGE and L-AVGE significantly decreased the mean Ki-67 labeling index, assessed as a measure of cell proliferation in the colonic mucosa. In addition, hepatic phase II enzyme glutathione S-transferase mRNA levels were higher in the H-AVGE group than in the HFDC group. These results suggest that both AVGP and AVGE may have chemopreventive effects on colorectal carcinogenesis under the HFD condition. Furthermore, the concentration of Aloe-sterols was similar between 3% AVGP and H-AVGE, suggesting that Aloe-sterols were the main active ingredients in this experiment.

Evaluation of peri-implant bone density changes in $Br{\aa}nemark$ implants by computer assisted densitometric image analysis (CADIA) (디지털 공제술을 이용한 $Br{\aa}nemark$ 임플란트 주위 골조직 분석)

  • So, Sung-Soo;Noh, Hyuen-Soo;Kim, Chang-Sung;Choi, Seong-Ho;Chae, Jung-Kiu;Kim, Chong-Kwan;Cho, Kyoo-Sung
    • Journal of Periodontal and Implant Science
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    • v.37 no.1
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    • pp.137-150
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    • 2007
  • CADIA(Computer-assisted densitometric image analysis) method is used to analyze bone density changes around the implants. The usefullness and reproducibility of the method was assessed. We tried to find out if there is any possibility to quantitiate and qualitify peri-implant bone density change as time passes. And we concluded that this newly developed linear analysis is efficient for analyzing peri-implant bone density change non-Invasively. In this study, 2152 machined $Br{\aa}nemark$ fixtures installed from 1994 to 2002 in the department of Periodontics, Dental hospital of College of Dentistry, Yonsei University were included. Of these fixtures 22 radiographically analyzable failed fixtures were used as experimental group, and 22 successful implants placed in the same patient were used as control group. 1. 57 out of 1635 machined $Br{\aa}nemark$ standard and Mk II implants system failed, the survival rate was 96.5%. And 11 out of 517 machined $Br{\aa}nemark$ Mk III and Mk IV implants system failed, the survival rate was 97.9%. Total survival rate was 96.8%. 2. 22 failed implants were used for the analysis, 10 of which failed before prosthetic treatment due to infection and overheating. 12 failed due to overload after prosthetic treatment, 63.6% of which failed during the early phase of functional loading, i, e. before 1 year of loading. 3. Bone density change values around coronal region of the failed implants were $-6.54{\pm}6.35$, middle region were $-3.53{\pm}5.78$, apical region were $-0.75{\pm}10.33$, resulting in average of $-3.71{\pm}8.03$. 4. Bone density change values around coronal region of the successful implants were $4.25{\pm}4.66$, middle region were $6.33{\pm}5.02$, apical region were $9.89{\pm}4.67$, resulting in average of $6.27{\pm}5.29$. 5. There was a statistically significant difference between two groups (p<0.01). In conclusion, the linear analysis method using computer-assisted densitometric image analysis could be a useful method for the analysis of implants, and could be used for future implant researchs.

Fortified Antioxidative Potential by Chrysoeriol through the Regulation of the Nrf2/MAPK-mediated HO-1 Signaling Pathway in RAW 264.7 Cells (생쥐 대식세포에서 HO-1 발현 유도를 통한 chrysoeriol의 항산화 효과)

  • Park, Chung Mu
    • Journal of Life Science
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    • v.28 no.1
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    • pp.43-49
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    • 2018
  • Chrysoeriol is a widespread flavone, and it is usually found in alfalfa, which has been used as a traditional medicine to treat dyspepsia, asthma, and urinary system disorders. Recently, analysis has been conducted on the anti-inflammatory activity of chrysoeriol, but information on its antioxidative capacity is limited. In this study, the antioxidative potential of chrysoeriol against oxidative damage and its molecular mechanisms were evaluated by analysis of the cell viability, reactive oxygen species (ROS) formation, and Western blots in the RAW 264.7 cell line. Chrysoeriol significantly scavenged lipopolysaccharide (LPS)-induced intracellular ROS formation in a dose-dependent manner, without any cytotoxicity. Heme oxygenase-1 (HO-1), a phase II enzyme that exerts antioxidative activity, was also potently induced by chrysoeriol treatment, which corresponded to the translocation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) into the nucleus. Moreover, mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) were analyzed due to their important role in maintaining cellular redox homeostasis against oxidative stress. As a result, chrysoeriol-induced HO-1 upregulation was mediated by extracellular signal - regulated kinase (ERK), c-Jun $NH_2$-terminal kinase (JNK), and p38 phosphorylation. To identify the antioxidative potential exerted by HO-1, tert-butyl hydroperoxide (t-BHP)-induced oxidative damage was applied and mitigated by chrysoeriol treatment, which was confirmed by the HO-1 selective inhibitor and inducer, respectively. Consequently, chrysoeriol strongly strengthened the HO-1-mediated antioxidative potential through the regulation of the Nrf2/MAPK signaling pathways.

Phase II Study of Paclitaxel and Cisplatin as Second-line Chemotherapy in Advanced Non-small Cell Lung Cancer (진행성 비소세포폐암에 대한 2차 화학요법으로 paclitaxel과 cisplatin의 제 2상 임상연구)

  • Seo, Yeoung-Tae;Kim, Bong-Seog;Go, Ji-Young;Choi, Dong-Suk;Choi, Seong-Ho;Kim, Hye-Jin;Ahn, Young-Mi;Roh, Yong-Ho;Lee, Kyung-Hee
    • Journal of Yeungnam Medical Science
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    • v.21 no.2
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    • pp.198-206
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    • 2004
  • Background: To evaluate the efficacy and safety of paclitaxel and cisplatin against advanced non-small cell lung cancer (NSCLC) as a second-line chemotherapy. Subjects and Methods: Twenty-five patients were enrolled. The patients received 200 $mg/m^2$ paclitaxel as a 3-hour intravenous infusion and 60 $mg/m^2$ cisplatin as 2D-minute intravenous infusion with vigorous hydration on day 1 every 28 days. The response was assessed every 2 cycles. Results: All 25 patients were assessed for their response and toxicity. Partial responses were observed in 5 patients. The overall response rate was 20%(95% confidence interval, 4%-36%) and the median response duration was 4.5(range, 2-11) months. The median time to progression was 3.3(range, 0-14) months. The median overall survival of all patients was 7.4(range, 1.3-39) months. The hematologic toxicities were minor and easily controlled. Conclusion: The combination chemotherapy of paclitaxel and cisplatin as a second-line treatment has a moderate efficacy with an acceptable toxicity in patients with advanced NSCLC.

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Phase II Study on Dose Escalating Schedule of Paclitaxel Concurrent with Radiotherapy in Treating Patients with Locally Advanced Non-small Cell Lung Cancer

  • Cui, Lin;Liu, Xing-Xiang;Jiang, Yong;Liu, Jian-Jun;Zhou, Xiang-Rong;He, Xue-Jun;Chen, Jue;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.4
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    • pp.1699-1702
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    • 2014
  • Objective: To evaluate clinical efficacy of a dose escalating schedule of paclitaxel concurrent with radiotherapy in treating patients with locally advanced non-small cell lung (NSCLC). Methods: Patients with locally advanced NSCLC were treated with conventional fractionated radiotherapy or three dimensional conformal radiotherapy (3 DCRT), concurrently with a dose escalating schedule of paclitaxel. All patients were divided into three groups, A with paclitaxel $30mg/m^2$, B with paclitaxel $60mg/m^2$ and C with paclitaxel $90mg/m^2$. Paclitaxel was repeated every week for a total of 4 or 6 weeks. Results: Among 109 patients, response rates were 68.8%, 71.1% and 71.8% (p>0.05) for group A (n=32), B (n=38), and C (n=39) respectively. Accordingly, disease control rates were 81.3%, 81.6% and 82.1% (p>0.05). Progression-free survival time was $8.0{\pm}5.0$ months, $11.6{\pm}6.1$ months, and $14.8{\pm}7.9$ months (p<0.05), respectively. Overall survival time was $15.4{\pm}7.6$ months, $18.2{\pm}8.0$ months, and $22.0{\pm}7.6$ months (p<0.05), one-year survival rates were 62.5%, 73.1% and 90.0% (p>0.05) and two-year survival rates were 31.3%, 38.5% and 50.0% (p<0.05). Main side-effects were bone marrow suppression, radiation related esophagitis and gastrointestinal reaction. Conclusion: In treating patients with NSCLC, concurrent chemoradiotherapy with paclitaxel improves early response compared with conventional fractionated radiotherapy or 3 DCRT. The survival rate was improved with the addition of paclitaxel, but there was an increase in adverse reactions when the dose of paclitaxel was increased.

Retardation Effect and Mobility of a Heavy Metal in a Sandy Soil (사질토양에서의 중금속의 지연효과와 이동성)

  • Kim, Dong-Ju;Baek, Doo-Sung
    • Journal of the Korean Society of Groundwater Environment
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    • v.5 no.3
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    • pp.155-161
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    • 1998
  • Retardation effect of heavy metals in soils caused by adsorption onto the surfaces of solids particles is well known phenomenon. In this study, we investigated the retardation effect on the mobility of a Zn in a sandy soil by conducting batch and column tests. The column test consisted of monitoring the concentrations of effluent versus time known as a breakthrough curve (BTC). We used NaCl and ZnCl$_2$ solutions with the concentration of 10 g/L as a tracer, and injected them respectively into the inlet boundary of the soil sample as a square pulse type, and monitored the effluent concentrations at the exit boundary under a steady state condition using an EC-meter and ICP-AES. The batch test was conducted based on the standard procedure of equilibrating fine fractions collected from the soil with various initial ZnCl$_2$ concentrations, and analysis of Zn ions in the equilibrated solutions using ICP-AES. The results of column test showed that i) the peak concentration of ZnCl$_2$analyzed by ICP was far less than that of either NaCl or bulk electrical conductivity and ⅱ) travel times of peak concentrations for two tracers were more less identical. The relatively low concentration of Zn can be explained by ion exchange between Zn and other cations, and possible precipitation of Zn in the form of Zn(OH)$_2$due to high pH range (7.0∼7.9) of the effluent. The identical result of travel times of peak concentrations indicates that the retardation effect is not present in the soil. The only way to describe the prominent decrease of Zn ion was to introduce decay or sink coefficient in the CDE model to account for irreversible decrease of Zn ions in the aqueous phase.

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Forsythia suspensa Extract Has the Potential to Substitute Antibiotic in Broiler Chicken

  • Han, X.;Piao, X.S.;Zhang, H.Y.;Li, P.F.;Yi, J.Q.;Zhang, Q.;Li, P.
    • Asian-Australasian Journal of Animal Sciences
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    • v.25 no.4
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    • pp.569-576
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    • 2012
  • Two experiments were conducted to investigate the potential for Forsythia suspensa extract (FSE) to substitute for antibiotic in broiler chicken. First, a well-diffusion assay procedure and a 2-fold dilution method were used to determine the bacteriostatic activity of FSE on Escherichia coli K88, staphylococcus aureus, and salmonella was assayed. An inhibitory effect of FSE was observed on the growth of these bacteria. This effect seems to be dose depended, which disappeared after 25.00, 12.50, 1.56 mg/ml. Second, a 42-d trial with 252 broiler chickens (d 1, $38.7{\pm}1.1$ g BW) was conducted to evaluate the effect of dietary supplementation of FSE in broiler chicken. The feeding program consisted of a starter diet from d 1 to 21 and a finisher diet from d 22 to 42. Dietary treatments included were: i) NC: negative control fed a corn-soybean meal based diet; ii) PC: positive control group fed based diet with chlortetracycline; and iii) FC: a test group fed with 100 mg FSE/kg diet. In this study growth performance did not differ among treatments during the starter period. However, dietary supplemental chlortetracycline and FSE increased (p<0.05) average daily gain (ADG), average daily feed intake (ADFI) compared with NC during the finisher and overall phase. Apparent digestibility of calcium on d 21, digestibility of energy and calcium on d 42 of FC was greater (p<0.05) than NC. Moreover, cecal Escherichia coli counts for birds from FC were lower (p<0.05) than NC. Dietary FSE supplementation also improved (p<0.05) villus height and villus height to crypt depth ratios in both duodenum and ileum and decreased (p<0.05) crypt depth in the duodenum. Duodenum villus height and villus height to crypt depth ratio in both duodenum and ileum from the FC group were also greater (p<0.05). Serum growth hormone and IGF-1 were not influenced by different treatments. Apparently, FSE has the potential to substitute for antibiotic in broiler chicken.

Luteolin-loaded Phytosomes Sensitize Human Breast Carcinoma MDA-MB 231 Cells to Doxorubicin by Suppressing Nrf2 Mediated Signalling

  • Sabzichi, Mehdi;Hamishehkar, Hamed;Ramezani, Fatemeh;Sharifi, Simin;Tabasinezhad, Maryam;Pirouzpanah, Mohammadbagher;Ghanbari, Parisa;Samadi, Nasser
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.13
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    • pp.5311-5316
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    • 2014
  • Nuclear factor erythroid 2-related factor 2 (Nrf2) has been recognized as a transcription factor that controls mechanisms of cellular defense response by regulation of three classes of genes, including endogenous antioxidants, phase II detoxifying enzymes and transporters. Previous studies have revealed roles of Nrf2 in resistance to chemotherapeutic agents and high level expression of Nrf2 has been found in many types of cancer. At physiological concentrations, luteolin as a flavonoid compound can inhibit Nrf2 and sensitize cancer cells to chemotherapeutic agents. We reported luteolin loaded in phytosomes as an advanced nanoparticle carrier sensitized MDA-MB 231 cells to doxorubicin. In this study, we prepared nano phytosomes of luteolin to enhance the bioavailability of luteolin and improve passive targeting in breast cancer cells. Our results showed that cotreatment of cells with nano particles containing luteolin and doxorubicin resulted in the highest percentage cell death in MDA-MB 231cells (p<0.05). Furthermore, luteolin-loaded nanoparticles reduced Nrf2 gene expression at the mRNA level in cells to a greater extent than luteolin alone (p<0.05). Similarly, expression of downstream genes for Nrf2 including Ho1 and MDR1 were reduced significantly (p<0.05). Inhibition of Nrf-2 expression caused a marked increase in cancer cell death (p<0.05). Taken together, these results suggest that phytosome technology can improve the efficacy of chemotherapy by overcoming resistance and enhancing permeability of cancer cells to chemical agents and may thus be considered as a potential delivery system to improve therapeutic protocols for cancer patients.

Phase II Study on Javanica Oil Emulsion Injection (Yadanzi®) Combined with Chemotherapy in Treating Patients with Advanced Lung Adenocarcinoma

  • Lu, Yan-Yan;Huang, Xin-En;Cao, Jie;Xu, Xia;Wu, Xue-Yan;Liu, Jin;Xiang, Jin;Xu, Lin
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4791-4794
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    • 2013
  • Purpose: To investigate the efficacy and safety of Javanica oil emulsion injection (Yadanzi$^{(R)}$) combined with pemetrexed and platinum (PP) for treating patients with advanced lung cancer. Patients and Methods: From June 2011 to June 2013, we recruited 58 patients with advanced lung cancer, and divided them into two groups. Twenty eight patients received Yadanzi$^{(R)}$ (from ZheJiang Jiuxu Pharmaceutical Co., Ltd.) together with PP chemotherapy (combined group), while the others were given only PP chemotherapy (control group). After two cycles of treatment, efficacy and safety of treatment were evaluated. Results: The overall respnse rate [(CR+PR+SD)/(CR+PR+SD+PD)] of the combined group was higher than that of control group (89.7% vs. 86.2%, p>0.05). Regarding rate of life improvement, it was 82.8% in combined group, and 51.7% in the control group (p<0.05). In terms of side effects, leukopenia in combined group was less frequent than that in control group (p<0.05). More patients in the control group were found to suffer liver toxicity. Conclusions: Javanica oil emulsion injection combined with chemotherapy could be considered as a safe and effective regimen in treating patients with advanced lung adenocarcinoma. It can improve the quality of life and reduce the possibility of leukopenia. Further clinical trials with a large sample size should be conducted to confirm whether addition of Yadanzi$^{(R)}$ to chemotherapy could increase the response rate, reduce toxicity, enhance tolerability and improve quality of life for patients with advanced lung cancer.

Anti-proliferative Effects of the Isothiocyanate Sulforaphane on the Growth of Human Cervical Carcinoma HeLa Cells (Sulforaphane에 의한 HeLa 인체자궁경부함세포의 증식 억제 기전 연구)

  • Park Soung Young;Bae Song-Ja;Choi Yung Hyun
    • Journal of Life Science
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    • v.15 no.3 s.70
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    • pp.397-405
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    • 2005
  • Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human cancer cells, however its molecular mechanisms are poorly understood. In the present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human cervical carcinoma HeLa cells. Treatment of HeLa cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells (9.83 fold of control). This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of cyclin A and cyclin-dependent kinase (Cdk)4 protein and concomitant induction of Cdc2, Cdk inhibitor p16 and p21. However, sulforaphane did not affect the levels of cyelooxygenases and telomere-regulatory gene products. Although further studies are needed, the present work suggests that sulforaphane may be a potential chemoprevetive/ chemotherapeutic agent for the treatment of human cancer cells.