http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Anti-VEGF Therapy with Bevacizumab - Limited Cardiovascular Toxicity
Yu, Jing,Cao, Xu-Fen,Zheng, Ye,Zhao, Rong-Cheng,Yan, Li-Qiu,Zhao, Lei,Wang, Jia-Wang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.24
Purpose: This analysis was conducted to evaluate cardiovascular toxicity of commonly used anti-VEGF therapeutic agent, bevacizumab, in treating patients with cancer. Methods: Clinical studies evaluating the efficacy and safety of bevacizumab-based regimens on response and safety for patients with cancer were identified using a predefined search strategy, allowing cardiovascular toxicity and other side effects of treatment to be estimated. Results: In bevacizumab based regimens, 4 clinical studies including 282 patients with advanced cancer (including gliomas, cervical, breast and ovarian cancer) were considered eligible for inclusion. These bevacizumab-based regimens included docetaxel, irinitecan and carboplatin. Systematic analysis suggested that, of 282 patients treated by bevacizumab based regimens, hypertension and thrombo-embolism occurred in 2.5% (7/282), while only 3 patients reported cardiovascular events (1.1%). No treatment related death occurred in bevacizumab based treatment. Conclusion: This systemic analysis suggests that bevacizumab based regimens are associated with reasonable and accepted cardiovascular toxicity when treating patients with gliomas, cervical, breast and ovarian cancer.
Yu Xiao,Fen Li,Anyuan Zheng,Qibing Chen,Fuhai Chen,Xiang Cheng,Zezhang Tao 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.8
Even though nasopharyngeal carcinoma (NPC) is not common worldwide, it is a major public health burden in endemic areas. Distant metastasis often leads to a poor prognosis for NPC; therefore, new and effective anticancer strategies are needed. Ginkgolic acid (GA) is small-molecule compound existing in Ginkgo biloba that has various biologically relevant activities, including antitumor properties; however, its effects and mechanism of action in NPC are unknown. The effects of GA on NPC and such underlying mechanisms were investigated using 5–8F and CNE2 cells and NP69 human immortalized nasopharyngeal epithelial cells in this study. Moreover, the xenograft models were built to examine GA's effection in vivo. GA treatment decreased the survival and invasive capacity of 5–8F and CNE2 and induced their apoptosis, which varied with dose; this was accompanied by downregulation of B cell lymphoma (Bcl)2, upregulation of Bcl2-associated X protein, and activation of poly-ADP ribose polymerase, and caspase-9/-3. G0/G1 phase arrest was induced by GA in NPCs. It also reduced the expression of cyclin-dependent kinase 6 and its regulators cyclin D2 and cyclin D3. GA inhibited the activation of protein kinase B/nuclear factor signaling; this effect was potentiated with GA and 5-fluorouracil (5-FU), which also enhanced 5-FU-induced apoptosis. In summary, GA may be effective as an adjuvant to conventional chemotherapy drugs in preventing the progression of NPC.
Kim, Jiseon,Min, Jee Sun,Kim, Doyun,Zheng, Yu Fen,Mailar, Karabasappa,Choi, Won Jun,Lee, Choongho,Bae, Soo Kyung Elsevier 2017 Journal of pharmaceutical and biomedical analysis Vol.134 No.-
<P><B>Abstract</B></P> <P>In this study, a simple and sensitive liquid chromatography-tandem mass spectrometry (LC–MS/MS) method for the quantification of <I>trans</I>-ε-viniferin in small volumes (10μl) of mouse plasma using chlorpropamide as an internal standard was developed and validated. Plasma samples were precipitated with acetonitrile and separated using an Eclipse Plus C<SUB>18</SUB> column (100×4.6mm, 1.8-μm) with a mobile phase consisting of 0.1% formic acid in acetonitrile and 0.1% formic acid in water (60:40v/v) at a flow rate of 0.5ml/min. A triple quadrupole mass spectrometer operating in positive ion mode with selected reaction-monitoring mode was used to determine <I>trans</I>-ε-viniferin and chlorpropamide transitions of 455.10→215.05 and 277.00→111.00, respectively. The lower limit of quantification was 5ng/ml with a linear range of 5–2500ng/ml (<I>r</I> ≥0.9949). All validation data, including the selectivity, precision, accuracy, recovery, dilution integrity, and stability, conformed to the acceptance requirements. No matrix effects were observed. The developed method was successfully applied to pharmacokinetic studies of <I>trans</I>-ε-viniferin following intravenous (2.5mg/kg), intraperitoneal (2.5, 5 and 10mg/kg), and oral (40mg/kg) administration in mice. This is the first report on the pharmacokinetic properties of <I>trans</I>-ε-viniferin. The results provide a meaningful basis for evaluating the pre-clinical or clinical applications of <I>trans</I>-ε-viniferin.</P> <P><B>Highlights</B></P> <P> <UL> <LI> First LC–MS/MS method for <I>trans</I>-ε-viniferin quantification in mouse plasma. </LI> <LI> A simple protein precipitation that allowed for efficient/reproducible recovery yields was used. </LI> <LI> The small plasma volume (10μl) supports the ability to examine pharmacokinetics in mice. </LI> </UL> </P>
Wang, Hua-Qian,Li, Dong-Li,Lu, Yu-Jing,Cui, Xiao-Xing,Zhou, Xiao-Fen,Lin, Wei-Ping,Conney, Allan H.,Zhang, Kun,Du, Zhi-Yun,Zheng, Xi Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.21
Acanthopanax trifoliatus (L) Merr (AT) is commonly used as an herbal medicine and edible plant in some areas of China and other Asian countries. AT is thought to have anticancer effects, but potential mechanisms remain unknown. To assess the anticancer properties of AT, we exposed prostate cancer cells to AT extracts and assessed cell proliferation and signaling pathways. An ethanol extract of AT was suspended in water followed by sequential extraction with petroleum ether, ethyl acetate and n-butanol. PC-3 cells were treated with different concentrations of each extract and cell viability was determined by the MTT and trypan blue exclusion assays. The ethyl acetate extract of the ethanol extract had a stronger inhibitory effect on growth and a stronger stimulatory effect on apoptosis than any of the other extracts. Mechanistic studies demonstrated that the ethyl acetate extract suppressed the transcriptional activity of NF-${\kappa}B$, increased the level of caspase-3, and decreased the levels of phospho-Erk1/2 and phospho-Akt. This is the first report on the anticancer activity of AT in cultured human prostate cancer cells. The results suggest that AT can provide a plant-based medicine for the treatment or prevention of prostate cancer.
Bae, Soo Hyeon,Park, Jung Bae,Zheng, Yu Fen,Jang, Min Jung,Kim, Sun Ok,Kim, Jeom Yong,Yoo, Young Hyo,Yoon, Kee Dong,Oh, Euichaul,Bae, Soo Kyung Taylor & Francis 2014 Xenobiotica Vol.44 No.12
<P><OL><LI><P>BST204, a purified ginseng dry extract containing a high concentration of racemic Rh2 and Rg3 mixtures, is being developed for supportive care use in cancer patients in Korea. This study investigates the pharmacokinetics and tissue distribution of BST204 in rats.</P></LI><LI><P>After oral administration of BST204, only the <I>S</I> epimers, S-Rh2 and S-Rg3, could be determined in rat plasma. The poor absorption of the <I>R</I>-epimers, R-Rh2 and R-Rg3, may be attributed to lower membrane permeability and extensive intestinal oxygenation and/or deglycosylation into metabolites. The AUC and <I>C</I><SUB>max</SUB> values of both S-Rh2 and S-Rg3 after BST204 oral administration were proportional to the administered BST204 doses ranged from 400 mg/kg to 2000 mg/kg, which suggested linear pharmacokinetic properties.</P></LI><LI><P>There were no statistically significant differences in the pharmacokinetics of S-Rh2 and S-Rg3 after oral administration of pure S-Rh2 (31.5 mg/kg) and S-Rg3 (68 mg/kg) compared with oral administration of BST204, 1000 mg/kg. These indicated that the presence of other components of BST204 extract did not influence the pharmacokinetic behavior of S-Rh2 and S-Rg3.</P></LI><LI><P>After oral dosing of BST204, S-Rh2 and S-Rg3 were distributed mainly to the liver and gastrointestinal tract in rats.</P></LI><LI><P>Our finding may help to understand pharmacokinetic characteristics of S-Rh2, R-Rh2, S-Rg3, and R-Rg3, comprehensively, and provide useful information in clinical application of BST204.</P></LI></OL></P>
Park, Jung Bae,Kim, Doyun,Min, Jee Sun,Jeong, Su,Cho, Doo-Yeoun,Zheng, Yu Fen,Yoon, Kee Dong,Bae, Soo Kyung Elsevier 2018 Food and chemical toxicology Vol.120 No.-
<P><B>Abstract</B></P> <P>Uva-ursi leaf is widely used to treat symptoms of lower urinary tract infections. Here, we evaluated the <I>in vitro</I> inhibitory effects of uva-ursi extracts on 10 major human UDP-glucuronosyltransferases (UGT) isoforms. Of the 10 tested UGT isoforms, uva-ursi extracts exerted the strongest inhibitory effect on UGT1A1-mediated β-estradiol 3-glucuronidation with the lowest IC<SUB>50</SUB> value of 8.45 ± 1.56 μg/mL. To identify the components of uva-ursi extracts showing strong inhibitory effects against UGT1A1, the inhibitory effects of nine major constituents of the extracts were assessed. Among the tested compounds, gallotannin exerted the most potent inhibition on UGT1A1, followed by 1,2,3,6-tetragalloylglucose; both demonstrated competitive inhibition, with K<SUB>i</SUB> values of 1.68 ± 0.150 μM and 3.55 ± 0.418 μM. We found that gallotannin and 1,2,3,6-tetragalloylglucose also inhibited another UGT1A1-specific biotransformation, SN-38-glucuronidation, showing the same order of inhibition. Thus, <I>in vitro</I> UGT1A1 inhibitory potentials of uva-ursi extracts might primarily result from the inhibitory activities of gallotannin and 1,2,3,6-tetragalloylglucose present in the extracts. However, in rats, co-administration with uva-ursi extracts did not alter the <I>in vivo</I> marker for UGT1A1 activity, expressed as the molar ratio of AUC<SUB>SN-38 glucuronide</SUB>/AUC<SUB>SN-38</SUB>, because plasma concentrations of gallotannin and 1,2,3,6-tetragalloylglucose may be too low to inhibit the UGT1A1-mediated metabolism of SN-38 <I>in vivo</I>. The poor oral absorption of gallotannin and 1,2,3,6-tetragalloylglucose in uva-ursi extracts might cause the poor <I>in vitro</I>-<I>in vivo</I> correlation. These findings will be helpful for the safe and effective use of uva-ursi extracts in clinical practice.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Uva-ursi is widely used to treat urinary tract infections. </LI> <LI> There is no information regarding inhibition of UGTs by uva-ursi. </LI> <LI> Strong UGT1A1 inhibition by uva-ursi <I>in vitro</I> is attributable to its two constituents, gallotannin and TeGG. </LI> <LI> But, uva-ursi did not affect UGT1A1 <I>in vivo</I> due to their poor oral absorption. </LI> </UL> </P>