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Explanation of the mechanism of carcinogenesis and syntheses of anticancer agents with high selectivity

science china Chemistry 2006年第1期49卷 44-62页

作者： DAI Qianhuan1,2 1. center of Chemistry and Bioengineering of Cancer Research, beijing Polytechnic university (Now known as beijing Univer-sity of Technology), beijing 100022, china 2. center of Environmental sciences, peking university, beijing 100871, china 1. center of Chemistry and Bioengineering of Cancer Research Beijing Polytechnic University Beijing 100022 China 2. center of Environmental sciences Peking University Beijing 100871 China

In 1979, the mechanism of chemical carcinogenesis, a challenging anddifficult scientific problem pending for a number of years, was explained by Dai Qianhuan. Themechanism named di-region theory predicted that a carcinogen always metabolizes to form a specialbi-functional alky-lating agent. This agent induces cross-linkages between the complementary basepairs in DMA and switches on initial mutageneses in genomes including point and frameshiftmutations. This, in turn, induces further deep mutageneses including the production of variouschimeric chromosomes, deletions and other aberrations found in genomes. In the end this initiatescarcinogenesis of the whole cell through the reverse transcription mechanism after a lengthyincubation period. Recently, this laboratory has verified that physical carcinogenesis, includingthe oncogenesis induced by radiation and asbestos as well as the carcinogenesis induced byendogenous factors such as estrogen or diethyl-stilbestrol switch on carcinogenesis by inducing theformation of cross-linkages between the complementary base pairs in DNA. Di-region theory has nowbeen supported by many experimental observations such as mutational spectra of various *** potential for carcinogenesis, teratogenesis, sterility and mutagenesis lumped together asgenetic toxicity appears to originate almost uniformly from the cross-linking between complementarybases, i.e. malignant cross-linking, which is in accordance with di-region theory. Other forms ofcross-linking between non-complementary bases, benign cross-linkings, show bi-functional alkylationanticancer activity but lack genetic toxicity. The predictable design and synthesis of a highselectivity anticancer agent with high efficacy and low genetic toxicity, a goal long pursued incancer chemotherapy, have been realized for the first time in this laboratory by inhibitingmalignant and heightening benign cross-linking using the principles of di-region theory. A series ofpatented new anticanc

关键词： mechanism of carcinogenesis, di-region theory, minoplatin, selectivity of anticancer agent, cross-linking between DNA bases, anticancer platinum complexes, predictive design of anticancer agent, second generation anticancer agent.

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Hormones and cancer

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Cell Research 2007年第4期17卷 277-279页

作者： Yongfeng Shang~1 ~1department of Biochemistry and Molecular Biology,peking university health science center,38 Xueyuan Rd,beijing 100083.china departmentofBiochemistryandMolecularBiology PekingUniversityHealthScienceCenter38XueyuanRdBeijing100083China

Estrogen exhibits a broad spectrum of physiologicalfunctions ranging from regulation of the menstrual cycleand reproduction to the modulation of bone density,brainfunction,and cholesterol ***,estrogenis also associated with pathological complications par-ticularly with the onset of gynaecological malignanciesincluding breast cancer and endometrial cancer;estrogenis now considered to be a classical etiological factor forbreast cancer and endometrial *** the early 1970s,it was reported that there was a 20-35% increase in incidence of endometrial cancer in WesternCaucasian women who had undergone estrogen therapy[1].Subsequently,a variety of clinical and epidemiologi-cal investigations,with support from studies in cell cultureand animal models,have demonstrated the association ofestrogen with the development and/or progression of *** 2002,the US National Toxicology Programlisted steroidal estrogens as carcinogens for the first *** report cites data from human epidemiologic studies thatshow an association between estrogen replacement therapyand an increase in the risk of endometrial cancer,as well asa less consistent increase in the risk of breast cancer.

关键词： gene NSABP Hormones and cancer ERE SERMs

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Inhibition of angiotensin Ⅱ and blockade of endothelin receptors reduce arterial calcification in rats

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Journal of Geriatric Cardiology 2004年第2期1卷 108-113页

作者： Juxiang LI~1 Shengying WU~1 Chunshui PAN~2 Yongfen QI~2 Bin GENG~1 Xiuhna LIU~~(1,2) Chaoshu TANG~1 1 department of physiology and Pathophysiology,peking university health science center,beijing 100083.china 2 Insitiute of Cardiovascular Research,peking university First Hospital,beijing 100034,china department of physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China Insitiute of Cardiovascular Research Peking University First Hospital Beijing 100034 China department of physiology and Pathophysiology Peking University Health Science Center Beijing 100083 China Insitiute of Cardiovascular Research Peking University First Hospital Beijing 100034 China

Objective To examine whether the two vascular paracrine/autocrine factors,angiotensin Ⅱ(Ang Ⅱ)and endothelin,participate in the pathogenesis of arterial *** Nicotine and vitamin D_3 treated rats were *** calcification was confirmed by using Von Kossa staining,measurement of calcium content, ^(45)Ca^(2+)uptake assay and alkaline phosphatase(ALP)*** plasma and vascular Ang Ⅱ and endothelin levels were measured by using *** and endothehn mRNA levels were determined by RT- *** The arterial calcium content,^(45)Ca^(2+)uptake and ALP activity were increased in calcification groups compared with control(P5)Ca^(2+)uptake and ALP *** addition,the plasma and aortic Ang Ⅱ and endothelin contents,and vascular angiotensinngen and endothelin mRNA expression were significantly up-regulated(P5). Conclusions These findings suggest that functional renin-angiotensin system and endothelin pathway are involved in vascular calcification,and that activation of these systems could potentiate pathogenesis of arterial calcification.(J Geriatr Cardiol 2004;1(2):108-113.)

关键词： aorta angiotensin Ⅱ endothelin-1 calcification

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Latest cosmological constraints on Cardassian expansion models including the updated gamma-ray bursts

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Research in Astronomy and Astrophysics 2011年第9期11卷 1019-1030页

作者： Nan Liang Pu-Xun Wu Zong-Hong Zhu department of Astronomy Beijing Normal University Beijing 100875 China center for High Energy Physics Peking University Beijing 100871 China center of Nonlinear science and department of Physics Ningbo University Ningbo 315211 China

We constrain the Cardassian expansion models from the latest observa- tions, including the updated Gamma-ray bursts （GRBs）, which are calibrated using a cosmology independent method from the Union2 compilation of type Ia supernovae （SNe Ia）. By combining the GRB data with the joint observations from the Union2 SNe Ia set, along with the results from the Cosmic Microwave Background radia- tion observation from the seven-year Wilkinson Microwave Anisotropy Probe and the baryonic acoustic oscillation observation galaxy sample from the spectroscopic Sloan Digital Sky Survey Data Release. we find significant constraints on the model oarameters of the original Cardassian model ΩM0=0.282-0.014^0.015,n=0.03-0.05^＋0.05 and n=-0.16-3.26^＋0.25,β=0.76-0.58^＋0.34 of the modified polytropic Cardassian model, which are consistent with the ACDM model in a l-or confidence region. From the reconstruction of the deceleration parameter q（z） in Cardassian models, we obtain the transition redshift ZT = 0.73 ± 0.04 for the original Cardassian model and ZT = 0.68 ± 0.04 for the modified polytropic Cardassian model.

关键词： gamma-rays bursts -- cosmology cosmological parameters

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Cardioprotective effects of ghrelin and des-octanoyl ghrelin on myocardial injury induced by isoproterenol in rats

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Acta Pharmacologica Sinica 2006年第5期27卷 527-535页

作者： LLian LI~2 Li-ke ZHANG~5 Yong-zheng PANG~(2.4) Chun-shui PAN~(3.4) Yong-fen QI~(3.4) Li CHEN~4 Xian WANG~(3,4) Chao-shu TANG~(3,4) Jing ZHANG~(2,4,6) ~2Institute of Cardiovascular Research,peking university First Hospital,beijing 100034,china:~3department of physiology and Pathophysiology,peking university health science center,beijing 100083.china ~4Key Laboratory of the Ministry of Education on Molecular Cardiology,beijing 100083.china:~5department of Pathophysiology,Capital university of Medicine,beijing 100054,china lnstituteofCardiovascularResearch PekingUniversityFirstHospitalBeijing100034China departmentofPathophysiology CapitalUniversityofMedicineBeijing100054China

Aim:To determine the cardioprotective action of ghrelin and des-octanoyl ghrelinin rats with isoproterenol-induced myocardial ***:Rats were subcu-taneously injected with isoproterenol （ISO;20,10,and 5 mg/kg） on d 1,2 and 3,respectively,and then 3 mg/kg for the next 7d with or without ghrelin or des-octanoyl-ghrelin （100μg/kg,twice daily）.Plasma ghrelin and growth hormonelevels were assayed using radioimmunoassay *** hormone secreta-gogue receptor （GHSR） and ghrelin mRNA were determined using *** binding capacity and the affinity for [3H]ghrelin were determined by re-ceptor binding ***:Compared with controls,ISO-treated rats showedsevere myocardial injury,cardiomegaly,infarction-like necrosis and massive fi-brosis with increases in irradiated-ghrelin （ir-ghrelin） content in plasma by 67%and myocardia by 66% and in the mRNA level in the myocardia by 93% （P5% （P5-fold （P<0.01）,with ghrelinadministration as compared with that in controls,but was unaltered in the des-octanoyl ghrelin ***:Myocardial ghrelin and GHSR were up-regulated during ISO-induced myocardial *** protective effect of ghrelinagainst ISO-induced cardiac function injury and fibrosis was more potent thanthat of des-octanoyl ghrelin,which suggests that ghrelin could be an endog

关键词： ghrelin des-octanoyl ghrelin myocardium fibrosis isoproterenol

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Enhancement of cardiomyocyte differentiation from human embryonic stem cells

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science china(Life sciences) 2010年第5期53卷 581-589页

作者： WANG YanXia1,2,CHEN GuiAn1,2,SONG TianRan1,2,MAO GenHong1,2 & BAI HaiYan1,2 1Reproductive Medicine center,peking university Third Hospital,beijing 100083.china 2Stem Cell Research center,peking university Third Hospital,beijing 100083.china 1. Reproductive Medicine center Peking University Third Hospital Beijing 100083 China2. Stem Cell Research Center Peking University Third Hospital Beijing 100083 China

Several approaches have been used to encourage the differentiation of cardiomyocytes from human embryonic stem ***,the differentiation efficiency is low,and appropriate culture protocols are needed to produce adequate numbers of cardiomyocytes for therapeutic cell *** study investigated the effects of serum on cardiomyocyte differentiation in suspension culture medium during embryoid body(EB) formation by human embryonic stem *** addition of ascorbic acid,dimethylsulfoxide and 5-aza-2'-deoxycytidine during days 5-7 at the EB-forming stage resulted in an increase in the numbers of rhythmically contracting clusters of derived *** with 0.1 mmol L-1 ascorbic acid alone,or more notably in combination with 10 μmol L-1 5-aza-2'-deoxycytidine,induced the formation of beating cells within *** of the beating clusters had spontaneous contraction rates similar to those found in human adults,and their contractile ac-tivity lasted for up to 194 days.

关键词： human embryonic stem cells cardiomyocyte differentiation serum ascorbic acid 5-aza-dC

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Expression,purification and serological analysis of hepatocellular carcinoma associated antigen HCA587 in insect cells

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World Journal of Gastroenterology 2003年第4期9卷 678-682页

作者： Bing Li Hong-Yan Wu Xiao-Ping Qian Yan Li Wei-Feng Chen Immunology department of peking university health science center,beijing,100083.china Immunology department of peking university health science center 38 Xueyuan Road Beijing 100083 China. wfchen@***

AIM: In order to assess hepatocellular carcinoma associated antigen HCA587 as a potential target for immunotherapy,the Bac-to-Bac expression system was used to express recombinant protein HCA587 in insect ***: The cDNA encoding HCA587 gene was cloned into donor vector pFasBacHtb and recombinant pFasBac Htb587 was transformed into competent cells *** Bacmid-587 was transfected into Sf9 insect cells using CELLFECTIN, Recombinant HCA587 protein was produced in Sf9 insect cells after infection with recombinant baculovirus, and was purified using Ni-NTA resin. Sera from HCC patients were also screened using recombinant protein ***: The molecular weight of the recombinant protein HCA587 expressed in insect cells was approximately *** blot results proved the recombinant protein HCA587had the similar antigenicity with its native *** analysis told that the rate of seroreactivity to HCA587 was not high in HCC ***: The recombinant protein HCA587 was successfully expressed and purified using Bac-to-Bac expression system. It paved the way for generation of specific antibody and investigation of immunohistochemical analysis and immune responses of HCC in the future.

关键词： HCA587抗原肝细胞癌血清学检查免疫疗法免疫组织化学

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A submillimeter observation and study of star-forming regions

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Chinese science Bulletin 2002年第1期47卷 16-21页

作者： JIANG Linhua, WU Yuefang & M. Millerdepartment of Astronomy, peking university, beijing 100871, china Chinese Academy of sciences-peking university Joint beijing Astrophysics center, beijing 100871, china I. Physikalisches Institut, Zulpicher Str department of Astronomy Peking University Beijing China Chinese Academy of sciences-peking university Joint beijing Astrophysics center Beijing China I. Physikalisches Institut Koeln 41 Germany

Using the 3-m radio telescope of KOSMA, we mapped 12CO (J = 3-2) lines for three molecular clouds, B35, S146 and TMC-2A. High-velocity molecular outflows are found in all these regions. The physical and dynamical pa-rameters of the outflows are derived, and their shapes and driving sources are analyzed. Contour maps of center veloci-ties show that the large scale systematic gradients exist in the three clouds. These observed motions are best explained by rotation after excluding the cause of outflows. Furthermore, in the core region of TMC-2A there is a velocity gradient in opposite direction from that of the large scale. It may be caused by magnetic braking. Finally, angular velocities of the clouds are calculated, and the effects of rotation against gravity and lowering the star-formation rate are also ana-lyzed.

关键词： dynamics of interstellar medium jets and outflows star formation.

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The synergistic effect of Hemokinin 1 in activating the peripheral mature B lymphocytes through ERK pathway

The synergistic effect of Hemokinin 1 in activating the peri...

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第六届全国免疫学学术大会

作者： Wei Wang Yu Zhang department of Immunology,peking university health science center,beijing 100083.china

Hemokinin 1 (HK-1) is an 11-amino peptide of tachykinin family,due to its distinctive

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A scoring model for predicting the prognosis of severe viral hepatitis

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中华医学杂志(英文版) 2005年第3期000卷 74-76页

作者： DING Hui-guo, XIANG Hai-ping, SHAN Jing, ZHOU Li, MA Bing, LIU Min and WANG Jun-taodepartment of GI & Hepatology, beijing Youan Hospital of Capital Medical university, beijing 100054, china department of health and Epidemiology, peking university health science center, beijing 100083, china department of GI & Hepatology Beijing Youan Hospital of Capital Medical University Beijing 100054 China department of health and Epidemiology Peking University Health Science Center Beijing 100083 China

The prognosis of patients with severe viral hepatitis is concerned by clinicians, patients and their relatives. Many factors may influence on the prognosis of patients with this disease. Many studies on the prognosis of severe viral hepatitis by multiple logistic regression analysis have shown generally consistent results.1-4 Previouly we established a scoring model of severe viral hepatitis （SMSVH） by logistic regression analysis.1 The aim of this study was to estimate prospectively the 6-month survival rate of patients with severe viral hepatitis using SMSVH.

关键词： severe viral hepatitis · survival analysis · prognostic factors

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