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Anti-tumor Effects of Penfluridol through Dysregulation of Cholesterol Homeostasis
Wu, Lu,Liu, Yan-Yang,Li, Zhi-Xi,Zhao, Qian,Wang, Xia,Yu, Yang,Wang, Yu-Yi,Wang, Yi-Qin,Luo, Feng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.1
Background: Psychiatric patients appear to be at lower risk of cancer. Some antipsychotic drugs might have inhibitory effects on tumor growth, including penfluridol, a strong agent. To test this, we conducted a study to determine whether penfluridol exerts cytotoxic effects on tumor cells and, if so, to explore its anti-tumor mechanisms. Methods: Growth inhibition of mouse cancer cell lines by penfluridol was determined using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Cytotoxic activity was determined by clonogenic cell survival and trypan blue assays. Animal tumor models of these cancer cells were established and to evaluate penfluridol for its anti-tumor efficacy in vivo. Unesterified cholesterol in cancer cells was examined by filipin staining. Serum total cholesterol and tumor total cholesterol were detected using the cholesterol oxidase/p-aminophenazone (CHOD-PAP) method. Results: Penfluridol inhibited the proliferation of B16 melanoma (B16/F10), LL/2 lung carcinoma (LL/2), CT26 colon carcinoma (CT26) and 4T1 breast cancer (4T1) cells in vitro. In vivo penfluridol was particularly effective at inhibiting LL/2 lung tumor growth, and obviously prolonged the survival time of mice bearing LL/2 lung tumors implanted subcutaneously. Accumulated unesterified cholesterol was found in all of the cancer cells treated with penfluridol, and this effect was most evident in LL/2, 4T1 and CT26 cells. No significant difference in serum cholesterol levels was found between the normal saline-treated mice and the penfluridol-treated mice. However, a dose-dependent decrease of total cholesterol in tumor tissues was observed in penfluridol-treated mice, which was most evident in B16/F10-, LL/2-, and 4T1-tumor-bearing mice. Conclusion: Our results suggested that penfluridol is not only cytotoxic to cancer cells in vitro but can also inhibit tumor growth in vivo. Dysregulation of cholesterol homeostasis by penfluridol may be involved in its anti-tumor mechanisms.
Wu, Ting-Ting,Wang, Zhi-Gang,Ou, Wu-Ling,Wang, Jun,Yao, Guo-Qing,Yang, Bo,Rao, Zhi-Guo,Gao, Jian-Fei,Zhang, Bi-Cheng Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24
Background: The study aimed to investigate the analgesic effect of a combination of intravenous flurbiprofen axetil and opioids, and evaluate the relationship between refractory pain relief and plasma ${\beta}$-endorphin levels in cancer patients. Materials and Methods: A total of 120 cancer patients was randomly divided into two groups, 60 patients took orally morphine sulfate sustained-release tablets in group A, and another 60 patients receiving the combination treatment of intravenous flurbiprofen axetil and opioid drugs in group B. After 7 days, pain relief, quality of life improvement and side effects were evaluated. Furthermore, plasma ${\beta}$-endorphin levels were measured by radioimmunoassay. Results: With the combination treatment of intravenous intravenous flurbiprofen axetil and opioids, the total effective rate of pain relief rose to 91.4%, as compared to 82.1% when morphine sulfate sustained-release tablet was used alone. Compared with that of group A, the analgesic effect increased in group B (p=0.031). Moreover, satisfactory pain relief was associated with a significant increase in plasma ${\beta}$-endorphin levels. After the treatment, plasma ${\beta}$-endorphin level in group B was $62.4{\pm}13.5pg/ml$, which was higher than that in group A ($45.8{\pm}11.2pg/ml$) (p<0.05). Conclusions: Our results suggest the combination of intravenous flurbiprofen axetil and opioids can enhance the analgesic effect of opioid drugs by increasing plasma ${\beta}$-endorphin levels, which would offer a selected and reliable strategy for refractory cancer pain treatment.
Wang, Weina,Wu, Qiuhua,Zang, Xiaohuan,Wang, Chun,Wang, Zhi Korean Chemical Society 2012 Bulletin of the Korean Chemical Society Vol.33 No.10
In this paper, a layered-carbon-$Fe_3O_4$ (LC-$Fe_3O_4$) hybrid material was synthesized through a facile one-pot solvothermal method and used as the adsorbent for the preconcentration of some phthalate esters (dimethyl phthalate, diethyl phthalate, diallyl phthalate, diisobutyl phthalate and benzyl butyl phthalate) in water samples. The effects of the adsorbent dosage, extraction time, the solution pH and salinity on the adsorption of the phthalate esters (PAEs) were investigated. The magnetic nanocomposite adsorbent could remove and enrich the PAEs from water samples efficiently. After the adsorption, the analytes were desorbed and then determined by high performance liquid chromatography-ultraviolet detection. Under the optimum conditions, the enrichment factors of the method for the analytes were in the range from 161 to 180. A linear response with peak area as the quantification signal was observed in the concentration range from 0.5 to $100ng\;mL^{-1}$. The limits of detection (S/N = 3) of the method were between 0.08 and $0.1ng\;mL^{-1}$. The method was suitable for the determination of trace phthalate esters in environmental water samples.
Wu, Chunxia,Zhao, Bin,Li, Yingli,Wu, Qiuhua,Wang, Chun,Wang, Zhi Korean Chemical Society 2011 Bulletin of the Korean Chemical Society Vol.32 No.3
A dispersive liquid-liquid microextraction based on solidification of floating organic droplet (DLLME-SFO) has been developed as a new approach for the extraction of trace copper in water and beverage samples followed by the determination with flame atomic absorption spectrometry. In the DLLME-SFO, 8-hydroxy quinoline, 1-dodecanol, and methanol were used as chelating agent, extraction solvent and dispersive solvent, respectively. The experimental parameters related to the DLLME-SFO such as the type and volume of the extraction and dispersive solvent, extraction time, sample volume, the concentration of chelating agent and salt addition were investigated and optimized. Under the optimum conditions, the enrichment factor for copper was 122. The method was linear in the range from 0.5 to $300\;ng\;mL^{-1}$ of copper in the samples with a correlation coefficient (r) of 0.9996 and a limit of detection of $0.1\;ng\;mL^{-1}$. The method was applied to the determination of copper in water and beverage samples. The recoveries for the spiked water and beverage samples at the copper concentration levels of 5.0 and $10.0\;ng\;mL^{-1}$ were in the range between 92.0% and 108.0%. The relative standard deviations (RSD) varied from 3.0% to 5.6%.
Weina Wang,Qiuhua Wu,Xiaohuan Zang,Chun Wang,Zhi Wang 대한화학회 2012 Bulletin of the Korean Chemical Society Vol.33 No.10
In this paper, a layered-carbon-Fe3O4 (LC-Fe3O4) hybrid material was synthesized through a facile one-pot solvothermal method and used as the adsorbent for the preconcentration of some phthalate esters (dimethyl phthalate, diethyl phthalate, diallyl phthalate, diisobutyl phthalate and benzyl butyl phthalate) in water samples. The effects of the adsorbent dosage, extraction time, the solution pH and salinity on the adsorption of the phthalate esters (PAEs) were investigated. The magnetic nanocomposite adsorbent could remove and enrich the PAEs from water samples efficiently. After the adsorption, the analytes were desorbed and then determined by high performance liquid chromatography-ultraviolet detection. Under the optimum conditions, the enrichment factors of the method for the analytes were in the range from 161 to 180. A linear response with peak area as the quantification signal was observed in the concentration range from 0.5 to 100 ng mL−1. The limits of detection (S/N = 3) of the method were between 0.08 and 0.1 ng mL−1. The method was suitable for the determination of trace phthalate esters in environmental water samples.
Cui, Zhi-Wen,Xia, Ye,Ye, Yi-Wang,Jiang, Zhi-Mao,Wang, Ya-Dong,Wu, Jian-Ting,Sun, Liang,Zhao, Jun,Fa, Ping-Ping,Sun, Xiao-Juan,Gui, Yao-Ting,Cai, Zhi-Ming Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.7
The molecular mechanisms involved in the progression of clear cell renal cell carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the relationships between expression of RALYL and clinical characteristics. In 41 paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to evaluate the expression of RALYL mRNA. RALYL protein levels were determined in 146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry. Statistical analysis was used to explore the relationships between expression of RALYL and the clinical characteristics (gender, age, tumor size, T stage, N stage, M stage, survival times and survival outcome) in ccRCC. In addition, these patients were follow-up period 64 months (range: 4~116months) to investigate the influence on prognosis. We found significantly differences between ccRCC tissues and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL. Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues showed significantly lower RALYL protein levels in ccRCC samples (${\chi}^2$-test, p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower level of RALYL expression had a poorer survival rate than those with a higher level of RALYL expression, significantly different by the log-rank test (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis factors for the overall survival of ccRCC patients. We demonstrated that the expression of RALYL was significantly low in ccRCC and correlated with a poor prognosis in a large number of clinical samples. Our findings showed that RALYL may be a potential therapeutic target as well as a poor prognostic factor.
Chunxia Wu,Bin Zhao,Qiuhua Wu,Chun Wang,Zhi Wang,Yingli Li 대한화학회 2011 Bulletin of the Korean Chemical Society Vol.32 No.3
A dispersive liquid-liquid microextraction based on solidification of floating organic droplet (DLLME-SFO)has been developed as a new approach for the extraction of trace copper in water and beverage samples followed by the determination with flame atomic absorption spectrometry. In the DLLME-SFO, 8-hydroxy quinoline, 1-dodecanol, and methanol were used as chelating agent, extraction solvent and dispersive solvent,respectively. The experimental parameters related to the DLLME-SFO such as the type and volume of the extraction and dispersive solvent, extraction time, sample volume, the concentration of chelating agent and salt addition were investigated and optimized. Under the optimum conditions, the enrichment factor for copper was 122. The method was linear in the range from 0.5 to 300 ng mL^(−1) of copper in the samples with a correlation coefficient (r) of 0.9996 and a limit of detection of 0.1 ng mL^(−1). The method was applied to the determination of copper in water and beverage samples. The recoveries for the spiked water and beverage samples at the copper concentration levels of 5.0 and 10.0 ng mL^(−1) were in the range between 92.0% and 108.0%. The relative standard deviations (RSD) varied from 3.0% to 5.6%.
Tie Jun Wang,Chen Guang Wang,Tie Jun Wang,Yan Gao,Chuang Zhi Wu,Long Long Ma 한국화학공학회 2008 Korean Journal of Chemical Engineering Vol.25 No.4
With naphthalene as biomass tar model compound, partial oxidation reforming (with addition of O2) and dry reforming of biomass fuel gas were investigated over nickel-based monoliths at the same conditions. The results showed that both processes had excellent performance in upgrading biomass raw fuel gas. Above 99% of naphthalene was converted into synthesis gases (H2+CO). About 2.8 wt% of coke deposition was detected on the catalyst surface for dry reforming process at 750 oC during 108 h lifetime test. However, no coke deposition was detected for partial oxidation reforming process, which indicated that addition of O2 can effectively prohibit the coke formation. O2 can also increase the CH4 conversion and H2/CO ratio of the producer gas. The average conversion of CH4 in dry and partial oxidation reforming process was 92% and 95%, respectively. The average H2/CO ratio increased from 0.95 to 1.1 with the addition of O2, which was suitable to be used as synthesis gas for dimethyl ether (DME) synthesis.