陈晓光
主要从事抗肿瘤药物的分子药理学研究及新药创制,主要研究领域为抗肿瘤药物研究新靶点—法尼基蛋白转移酶, 基质金属蛋白酶、TGF-b、还氧合酶II、MAPK以及细胞内核酸库等方面的研究。
个性化签名
- 姓名:陈晓光
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学术头衔:
博士生导师
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学科领域:
细胞生物学
- 研究兴趣:主要从事抗肿瘤药物的分子药理学研究及新药创制,主要研究领域为抗肿瘤药物研究新靶点—法尼基蛋白转移酶, 基质金属蛋白酶、TGF-b、还氧合酶II、MAPK以及细胞内核酸库等方面的研究。
陈晓光,男,一直从事肿瘤分子药理学研究与新药开发。1995年曾获得首届DEBIO PHARM-CCRF中国奖一等奖,今年又获得DEBIO PHARM-CCRF中国奖三等奖。1996年3月至1996年11月在日本大阪市立大学医学部第二生化学教室作为客员助教授从事法尼基蛋白转移酶及其抑制剂方面的研究,有关论文发表在1997年Anticancer Res.和JANPR,当年在美国洛杉机举行的肿瘤预防与化学治疗研讨会邀请此篇论文作者就法尼基转移酶及其抑制剂作大会报告;1997年5月至1997年8月在瑞士Vaudois大学附属医院癌研究中心作为访问学者从事高效液相测细胞内核酸库在抗肿瘤药物应用方面的共同研究,其研究论文L731抗肿瘤及放射增敏作用和对肿瘤细胞内核酸库的影响分别发表在1998年Cancer Res和1999年Analy. Biochem,L731目前正在欧洲上市。2000年到2001年在美国亨利福特医学中心福特医院神经科学主要从事干细胞的研究,其研究论文发表在J. Neuroscience Res. 、Neuropathology、Neurology、Hematology。近年来,主要从事抗肿瘤药物的分子药理学研究及新药创制,主要研究领域为抗肿瘤药物研究新靶点—法尼基蛋白转移酶, 基质金属蛋白酶、TGF-b、还氧合酶II、MAPK以及细胞内核酸库等方面的研究。主持完成了1个Ⅰ类、2个Ⅱ类、3个Ⅲ类抗肿瘤新药药效学及毒理学研究,目前正在主持1个Ⅰ类(有自主知识产权)新药进入临床前全面开发,尚有几个新药侯选物正在临床前研究和验证的不同阶段。到目前为止,在国内外学术刊物上已发表学术论文70余篇;申请国内、国际化学发明专利8项;承担国家级项目10余项,其中包括“973”、“863”、国家科技部“技术平台”、多项国家自然科学基金等,此外还承担北京市重大科技项目两项和北京市自然科学基金项目等。目前主要学术任职为;中国抗癌协会、抗癌药物专业委员会委员,中国癌症研究基金会理事,国家科技部医药科技发展项目评审委员,国家“十五”攻关项目专家组成员,SFDA新药评审专家库成员,SFDA保健品评审专家,中国新医药博士联谊会理事,北京生物技术和新医药产业促进中心新药项目评审专家,中国医学科学院中国协和医科大学学位评定委员会委员、学术委员会委员,中华肿瘤学杂志等编委。
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陈晓光, Dan Huanga, Yazhuo Zhangb, Xiaoguang Chena, *
Journal of Chromatography B, 784 (2003) 101-109,-0001,():
-1年11月30日
he HPLC columns were 18 kept at 27.8C. The mobile phase was delivered at a flow-rate of 1.0 ml/min, with the following stepwise gradient elution program: A-B (60:40) at 0 min→(40:60) at 30 min→(40:60) at 60 min. Solvent A contained 10 mM tetrabutylammonium hydroxide, 10 mM KH PO and 0.25% MeOH, and was adjusted to pH 6.9 with 1 M HCl. Solvent B consisted of 5.6 mM 24 tetrabutylammonium hydroxide, 50 mM KH PO and 30% MeOH, and was neutralized to pH 7.0 with 1 M NaOH. The 24 calibration curves (r.0.99) of the components in cell extracts were established with their aqueous standards. The average within-day precision for the nine compounds was 0.9%, and the average day-to-day precision was 5.0%. The detection limits (pmol) of the nine reagents were 1.39 (ADP), 4.32 (CTP), 15.5 (dCTP), 2.38 (GTP), 4.42 (UTP), 9.45 (dGTP), 14.6 (dTTP), 2.44 (ATP) and 11.8 (dATP). The recovery of this method for the standards ranged from 82.4 to 120.5%. The results for the detection of nucleotide pools in 16 normal and tumor cell lines were presented. In conclusion, this simplified analytical method enables the simultaneous quantitation of NTP and dNTP in cell or tissue extracts and may represent a valuable tool for the detection of minute alterations of intracellular NTP/dNTP pools induced by anticancer/antiviral drugs and diseases.
Tumor cells, Nucleoside triphosphates
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陈晓光, Yl Li, , Xiaoyi Yang, Jieli Chen, Lei Wang, Ying Wang, Chunling Zhang, Xiaoguang Chen, Mark Katakowski, Tom Mikkelsen, Mci Lu, *, Michael Chopp
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-1年11月30日
We constructed a biologicmaterial composedoffetal ratbrain cells (neurospheres) and adult rat bone marrow stromal cells (MSCs), designated as NMCspheres Adult rats were subjected to 2 hours of middle cerebral artery occlusion (MCAo) and implanted with cultured prelabeled NMCspheres (n=6), neurospheres (n=5) or MSCs (n=6) into the ischemic penumbra at 24 hours after MCAo. Control adult rats (n=10) were subjected to MCAo alone. In vitro within the NMCspheres, MSCs rapidly fonned a process network with intact neural cells compared with a necrotic core within neurospheres alone An in vivo rat corneal assay demonstrated that NMCspheres enhanced angiogenesis compared to MSCs and neurospheres Neurological functional recovery after stroke was enhanced in rats trcated with NMCspheres, compared to rats with neurosphere or MSC treatments by day 7 and day 14 after transplantation. The NMCspheres are a new compositc material that may be employed in the treatment of stroke
stroke, neurosphere, bone marrow stromal cells, a new cell aggregate model, rat
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陈晓光, Philippe A. Coucke, , Laurent A. Decosterd, Ye-Xiong Li, Eliane Cottin, Xiaoguang Chen, Lin-Quan Sun, Sabine Stern, Nicolas Paschoud, and Juliana Denekamp
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-1年11月30日
(E)-2'-Deoxy-(fluoromethylene) cytidine (FMdC) is known as an inhibitor of ribonucleoside diphosphate reductase, a key enzyme in the de novo pathway of DNA synthesis. FMdC was tested as a modifier of radiation response in vitro on a human colon carcinoma cell line (WiDr), and the observed radiosensitization was confirmed on two human cervix cancer cell lines (C33-A and SiHa). Using the clonogenic assay, the effect ratio (ER) at a clinically relevant dose level of 2 Gy was 2.10 (50nM FMdC), 1.70 (30nM FMdC), and 1.71 (40nM FMdC) for the three cell lines WiDr, C33-A, and SiHa, respectively. A more detailed analysis of the importance of timing and concentration of FMdC was done on the WiDr cell line alone, yielding an increased ER (2Gy) with increasing concentration and duration of exposure to the drug, ranging from 1.0 (6h) to 1.8 (72h) at 30 nM FMdC and from 1.2 (6h) to 3.5 (24h) at 300nM. We investigated the effect of FMdC on the cellular deoxynucleotide triphosphate pool in WiDr cells and demonstrated a marked depletion of dATP and a significant rise of TTP levels. Cell cycle analysis showed early S-phase accumulation induced by FMdC alone, G2-M block induced by irradiation alone, and an increased accumulation of cells in G2-M if both modalities are used. Our data suggest that FMdC is a radiation response modifier in vitro on different cancer cell lines. The observed radiosensitization may in part be explained by alteration of the deoxynucleotide triphosphate pool, which is consistent with the effect of FMdC on ribonucleoside diphosphate reductase.
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陈晓光, Xin Zhao, a, †, Jun Gu, b, Dali Yin b and Xiaoguang Chen a, *
Bioorganic & Medicinal Chemistry Letters, 2004, 14, 4767-4770,-0001,():
-1年11月30日
Three novel taxinine analogues were prepared and tested for their activity as multidrug resistance (MDR) reversal agents in comparison with verapamil. In vitro testing demonstrated that compounds 8-10 possess MDR-reversal activity in the KB/V cell line. Half-hour after treatment with 5, 10, and 20lmol/L compound 9, the intracellular rhodamine123 concentration increased 2.3, 2.9, and 3.2-fold, respectively, higher than 1.88-fold of 10lmol/L verapamil in KB/V cell line. In vivo studies with VCR-resistant KB/V tumor xenografts showed that compound 9 in combination with VCR significantly inhibited tumor growth. Treatment with VCR or 9 alone did not result in growth inhibition. These results reveal that three taxinine analogues are good modifiers of MDR in tumor cells.
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陈晓光, Bu-Bing Zeng, [a], YikangWu, Sheng Jiang, Qian Yu, Zhu-Jun Yao, Zhong-Hai Liu, [b], Hong-Yan Li, Yan Li, Xiao-Guang Chen, [b] and Yu-Lin Wu*[a]
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-1年11月30日
A class of structurally simplified analogues of the naturally occurring annonaceous acetogenins were developed, amongst which some non-THF analogues showed remarkable cytotoxicities against tumor cell lines, as well as good selectivity between human tumor cells and normal cells. The synthetic routes were significantly shortened because of the removal of the chiral centers bearing the THF rings on the natural templates. This simplification also provides access to the parallel synthesis of these mimics by a ombinatorial strategy. The remaining stereogenic centers at the positions-to the ethereal links were introduced by the Chiron approach from the easily accessible chiral building blocks 6a and/or 6b, made in turn from-ascorbic acid or-mannitol, while the one in the butenolide segment was taken from-lactate. All four diastereomeric non-THF analogues 2a-2d showed remarkable activity against the HCT-8 cell line, and better differentiation was found when testing against the HT-29 cell line. It was also discovered that both the butenolide and ethylene glycol subunits play essential roles in the cytotoxicities against tumor cell lines, while the 10-substituted hydroxy group and the absolute configuration of methyl group at the butenolide moiety are less important for their activity.
annonaceous acetogenins, symmetric synthesis, cytotoxicity, natural products, structure-activity relationships
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陈晓光, L.A. Decosterd, *, , E. Cottin, X. Chen, F. Lejeune, R.O. Mirimanoff, J. Biollaz, * and P. A Coucke
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-1年11月30日
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陈晓光, Jieli Chen, , Yi Li, Mark Katakowski, Xiaoguang Chen, Lei Wang, Dunyue Lu, Mei Lu, Subhash C. Gautam, and Michael Chopp, *
Journal of Neuroscience Research 2003, 73, 778-786,-0001,():
-1年11月30日
The present study investigates the induction of neurogenesis, reduction of apoptosis, and promotion of basic fibroblast growth factor (bFGF) expression as possible mechanisms by which treatment of stroke with bone marrow stromal cells (MSCs) improves neurological functional recovery. Additionally, for the first time, we treated cerebral ischemia in female rats with intraveneous administration of MSCs. Female rats were subjected to 2 hr of middle cerebral artery occlusion (MCAo), followed by an injection of 3
marrow stromal cells, subventricular zone, MCAO, cerebral ischemia, apoptosis,, female rat
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陈晓光, Xiaoguang Chen, , Mark Katakowski, Yi Li, Dunyue Lu, Lei Wang, Lijie Zhang, Jieli Chen, Yongxian Xu, Subhash Gautam, Asim Mahmood, and Michael Chopp, *
Journal of Neuroscience Research 2002, 69, 687-691 ,-0001,():
-1年11月30日
Treatment of traumatic brain injury (TBI) with bone marrowstromal cells (MSCs) improves functional outcome in the rat. However, the specific mechanisms by which introduced MSCs provide benefit remain to be elucidated. Currently, the ability of therapeutically transplanted MSCs to replace injured parenchymal CNS tissue appears limited at best. Tissue replacement, however, is not the only possible compensatory avenue in cell transplantation therapy. Various growth factors have been shown to mediate the repair and replacement of damaged tissue, so trophic support provided by transplanted MSCs may play a role in the treatment of damaged tissue. We therefore investigated the temporal profile of various growth factors, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor (HGF), within cultures of human MSCs (hMSCs) conditioned with cerebral tissue extract from TBI. hMSCs were cultured with TBI extracts of rat brain in vitro and quantitative sandwich enzyme-linked immunosorbent assays (ELISAs) were performed. TBI-conditioned hMSCs cultures demonstrated a time-dependent increase of BDNF, NGF, VEGF, and HGF, indicating a responsive production of these growth factors by the hMSCs. The ELISA data suggest that transplanted hMSCs may provide therapeutic benefit via a responsive secretion of an array of growth factors that can foster neuroprotection and angiogenesis.
marrow stromal cells, traumatic brain injury, neurotrophins, angiogenesis, growth factors
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【期刊论文】Cancer chemopreventive and therapeutic activities of red ginseng
陈晓光, Chen Xiaoguang a, *, Liu Hongyan a, Lei Xiaohong a, Fu Zhaodi a, Li Yan a, Tao Lihua b, Han Rui a
Journal of Ethnopharmacology 1998, 60, 71-78,-0001,():
-1年11月30日
Red ginseng extract A and B are the active components of Panax ginseng. Red ginseng is a classical traditional Chinese medicine. Among Chinese herbs, red ginseng has been considered as one of the tonics. Many studies indicated that red ginseng could enhance immune function of the human body. The effects of red ginseng extracts on transplantable tumors, proliferation of lymphocyte, two-stage model and rat liver lipid peroxidation were studied. In a two-stage model, red ginseng extracts had a significant cancer chemoprevention. At 50-400mg/kg, they could inhibit DMBA/Croton oil-induced skin papilloma in mice, decrease the incidence of papilloma, prolong the latent period of tumor occurrence and reduce tumor number per mouse in a dose-dependent manner. Red ginseng extract B could effectively inhibit the Fe 2+/cysteine-induced lipid peroxidation of rat liver microsome, suggesting that red ginseng extract B has a stronger antioxidative effect than that of extract A. The results indicated that red ginseng extracts (50: 400mg/kg) could significantly inhibit the growth of transplantable mouse sarcoma S180 and melanoma B16. Red ginseng extracts A (0.5mg/ml) and B (0.1 and 0.25mg/ml) might effectively promote the transformation of T lymphocyte, but there was no influence on lymphocyte proliferation stimulated by concanavalin A. This suggests that red ginseng extracts have potent tumor therapeutic activity and improve the cell immune system.
Red ginseng, Transplantable tumor, Tlymphocyte proliferation, Tumorigenesis, Lipid peroxidation
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