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Chinese Science Bulletin 1997年第3期42卷 231-234页

作者： Gao, ZQ Gao, ZP Liu, XF Department of Pathology Beijing Medical University Beijing China

NON-SMALL-CELL lung cancer (NSCLC) accounts for 75%—80% of all lung cancers. Chemotherapy.is the basic treatment for the patients with NSCLCs, which are often resistant to drugs because of tumor multidrug resistance, the main cause of lower cure rate. Overexpression of P-glycoprotein (Pgp), the product of multidrug resistance gene (MDR1), is the main mechamsm by which tumor produces multidrug resistance. MDR1 gene is known to induce multidrug resistance. MDR1 antisense RNA could inhibit the expression of MDR1 gene and reverse the multidrug resistance in multidrug-resistant human lung cancer. In clinical studies,

关键词： lung cancer orthotopic model MDR1 ribozyme reversal of drug resistance therapy.

Construction and expression of inverted configuration of retroviral vector containing intron 1 of hFIX

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Chinese Science Bulletin 1998年第4期43卷 315-318页

作者： Wang Hongwei Bao Yun Xin Yongna Yang Xiaoqin Shi Qian Lu Daru Qiu Xinfang Xue Jinglun Fudan Univ Inst Genet Shanghai 200433 Peoples R China

Intron was found to play an important role in improving gene expression. To improve the human factor IX(hFIX) expression level in hemophilia B gene therapy.study, the retroviral vector containing intron 1 of hFIX gene was constructed in forwarded configuration, but the intron 1 was found spliced in virus particles by RT_PCR detection. So the inverted configuration vector G1NaPAi′IX was suggested and constructed on the basis of SNMBAIXm and transfected into PA317. Then C2C12 cells were transfected using the above virus supernatant and the G418_resistant clones were selected. PCR and RT_PCR detection found that intron 1 structure existed in C2C12 clones and retroviral particles. And the expression level of inverted vector was 3 times higher than that of forwarded vector. These results showed that the inverted configuration vector was in deed able to avoid splicing of intron 1 during the process of retroviral packaging and improved the expression level of hFIX protein.

关键词： hFIX cDNA intron 1 retroviral vector gene therapy.

Directional migration of leukocytes: their pathological roles in inflammation and strategies for development of anti-inflammatory therapies

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Cell Research 2001年第2期11卷 85-88页

作者： GENG JIAN Guo Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China Institute of Biochemistry and Cell Biology Shanghai Institutes for Biological Sciences Chinese Academy of Sciences Shanghai China

Directional migration of leukocytes is indispensable to innate immunity for host defense. However, recruitment of leukocytes to a site of tissue injury the constitutes a leading cause for inflammatory responses. Mechanistically, it involves a cascade of cellular events precisely regulated by temporal and spatial present tation of a repertoire of molecules in the migrating leukocytes and their surroundings (microenvironments). Here I will summarize the emerging evidence that has shed lights on the underlying molecular mechanism for directional migration of leukocytes, which has guided the therapeutical development for innovative anti-inflammatory medicines.

关键词： Directional cell migration leukocytes inflammation therapy.

Bispecific antibody and its clinical applications in cancer

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Chinese Science Bulletin 2001年第5期46卷 353-358页

作者： Yuanfu Xu Chunzheng Yang Zhenping Zhu Chinese Acad Med Sci Peking Union Med Coll Inst Hematol Natl Lab Expt Hematol Tianjin 300020 Peoples R China

Bispecific antibody (BsAb) usually consists of two different antigen-binding arms, by which it is capable of simultaneously binding to target cells and effector cells, and can directly mediate the killing of target cells by retargeting and activating effector cells. The development of BsAb research goes through three main stages: chemical cross-linking of murine-derived monoclonal antibody, hybrid hy-bridomas and engineered BsAb. Among them, engineered BsAb has more formats than the other two, such as diabody, ScdHLX, ScZip, ScCH3, ScFab and BsIgG, etc. Compared with former murine-derived BsAbs, engineered BsAb has lower immunogenicity and stronger penetrating capacity, and currently, some of them appear suitable for clinical application in yields and qualities. Up to now, several phase I and phase II clinical studies of BsAb, for instance, some (Fab’)2 and Diabodies, have been performed. Among those BsAbs, anti-CD3/anti-tumor BsAbs is most common, they not only can activate T cell and induce CD3AK

关键词： bispecific antibody genetic engineering tumor therapy.

Recombinant soluble TRAIL induces apoptosis of cancer cells

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Chinese Science Bulletin 2001年第24期46卷 2073-2077页

作者： LI Lianyun HU Jiancheng BIN Lianghua LI Lixia ZHA Jikun XU Liangguo ZHANG Zhen ZHAI Zhonghe SHU Hongbing College of Lite Sciences Peking UniversityBeijing 100871China National Jewish Medical and Research Center 1400 Jackson Street DenverColorado 80206USA

TRAIL is a tumor necrosis factor family member that selectively induces apoptosis of cancer cells but not of normal cells. To develop TRAIL into a potential cancer drug, three different sizes of soluble TRAIL fragments, including sTRAIL(74 - 281), sTRAIL(95 - 281) and sTRAIL(101-281), were expressed in E. coli and purified to homogeneity. Apoptosis assays indicated that sTRAIL(95-281) and sTRAIL(101-281), but not sTRAIL(74-281), can potently induce apoptosis of various cancer cell lines in 6 h, suggesting that the N-terminal fragment of aa101 has inhibitory effect on TRAIL-induced apoptosis. Moreover, we found that some cancer cells were resistant to TRAIL and the resistant cells could be converted into sensitive cells by treatment with the protein synthesis inhibitor cycloheximide, suggesting that one or more short-lived proteins are responsible for cells’ resistance to TRAIL.

关键词： TRAIL. apoptosis cancer therapy.

THE OPTICAL PROPERTIES OF PHEOPHORBIDE A

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Chinese Science Bulletin 1990年第22期35卷 1886-1890页

作者：孟继武侯尚公黄世华徐叙瑢 Changchun Institute of Physics Academia Sinica Changchun 130021 PRC

Photochemical therapy.has become a new area in treating malignant tumour with photosensitive medicines. In recent years, a new photosensitive medicine phcophorbide A (PhA) is developed, with curative effect ten times as high as that of Hematoporphyrin. In this note, the method of preparing PhA from pteridophyte is reported, the electronic spectra of PhA is qualitatively analyzed by HMO figure theory and the mechanism of photochemically treating cancer is discussed.

关键词： pheophorbide A singlet oxygen photochemical therapy.

Intracellular expression of a single-chain antibody directed against type IV collagenase inhibits the growth of lung cancer xenografts in nude mice

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Science China(Life Sciences) 2000年第4期43卷 433-441页

作者：王维刚张胜华李毅徐琳娜周京华甄永苏 Department of Oncology Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100050 China

It was documented that type IV collagenase with two subtypes of 72 ku/MMP-2 and 92 ku/MMP-9 plays an important role in tumor invasion and metastasis. The endoplasmic reticulum (ER)- retained, single chain Fv antibody fragment (scFv) was used to inhibit the function of type IV collagenase. For expression in mammalian cells, the assembled scFv M97 gene with ER retention signal encoding 6 additional amino acids (SEKDEL) was reamplified by PCR. The amplified fragments were cloned into the pcDNA3.1 vector. The resulting plasmid was sequenced and then introduced into PG cells, a highly metastatic human lung cancer cell line, by lipofectAMINE method. The result of intrabody gene therapy.showed that type IV collegenase expression was down regulated significantly as measured by ELISA. The biological behavior of PG cell, such as the ability of in vitro invasion through Matrigel, colony formation on soft agar, was also inhibited by scFv M97 transfection. Animal experiments in a xenograft model of human lung

关键词： intracellular antibody (intrabody) type IV collagenase cancer invasion and metastasis gene therapy.

THE THERMAL EFFECT OF FERRIMAGNETIC RESONANCE AND ITS PROBABLE APPLICATION IN MICROWAVE HYPERTHERMIA IN CANCER therapy

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Chinese Journal of Biomedical Engineering(English Edition) 1993年第1期2卷 26-32页

作者： Chen Guozhang, Wu Ganghua,Dong Dingwei Zhejiang Medical University Zhejiang Institute of Techonology

To improve microwave hyperthevmia in cancer therapy. the thermal effect of fer-rimagnetic resonance (FMR) during microwave irradiation was studied. Resonant temperatureelevation (RTE) of single crystal grain and polycrystal powder of resonant media was measuredalone and in imitative muscle and egg white and in mice. The results indicated that the RTE produced by FMR could be used to improve penetrationdeepness, heating selectivity and temperature distribution of microwave hyperthermia in cancertreatment. It was expected that the potential function of the FMR heating system would be ex-ploited greatly for cancer therapy. and then magnetically guided microwave hyperthermia thera-py, chemotherapy. radiotherapy.and immunotherapy.might he combined multiply within this sys-tem by means of the static magnetic field (SMF) and magnetic microcarrier. Limitation of reso-nant heating was also discussed in this paper.

关键词： magnetical guidance ferrimagnetic resonance microwave hyperthermia cancer therapy.

Combined therapy.of p53-wt and drug in an orthotopic multidrug-resistant human lung cancer model

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Science China(Life Sciences) 1997年第3期40卷 232-237页

作者：高振强高志萍张涛 Department of Pathology Beijing Medical University Beijing 100083 China

Balb/c nu/nu mice were inoculated intratracheally with multidrug-resistant human lung cancer cells GLK containing p53 mutation at codon 245 and treated with intratracheal instillation of p53-wt retroviral vector (pDOR53W) to increase cell chemosensitivity, and then with intraperitoneal injection of doxorubicin. 30 d after tumor cell inoculation, 75% of the control mice showed macroscopic tumors in the lung. Sole pDOR53W suppressed GLK tumor formation in 68 % of mice; sole doxorubicin 33. 3 % , but the combination of pDOR53W and doxorubicin 88.9%. The exogenous p53 sequence was detected and confirmed in the tumor that grew after treatment with pDOR53W retroviral vector by PCR and Southern blot hybridization with p53 cDNA. These results suggested that di-rect administration of a retroviral vector expressing p53-wt combined with treatment of anticancer agent was an effec-tive therapeutic method for multidrug-resistant human lung cancer.

关键词： human lung cancer drug resistance p53 gene anticancer drug therapy.

Therapeutic effects on experimental metastatic tumor-bearing mice by vaccination with GM-CSF gene-modified and tumor antigen-pulsed macrophages

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Science China(Life Sciences) 1998年第1期41卷 107-112页

作者：于益芝曹雪涛雷虹张明徽章卫平朱学军叶天星王建莉 Department of Immunology Second Military Medical University Shanghai China

Macrophages, with potent cytotoxic and antigen presenting activities, can be used in cancer treatment. The biological characteristics and antitumor effect of GM CSF gene modified and tumor antigen pulsed macrophages were investigated. The high levels of GM CSF could be detected in the supernatants of macrophages after gene transfer. The cytotoxicity and the expression of MHC class II molecules of the gene modified macrophages increased significantly and the antigen presenting ability was enhanced. The gene modified macrophages were then pulsed with tumor antigen and used to treat the experimental pulmonary metastastic mice. The number of pulmonary metastases was reduced significantly and the cytotoxicity of the CTL induced from the splenocytes of the tumor bearing mice also increased. The results demonstrated that adenovirus mediated GM CSF gene transfer can activate macrophages to some extent and GM CSF gene modified, antigen pulsed macrophages may be a new type of effective effector cells in the immunogene therapy.of cancer.

关键词： granulocyte macrophage colony stimulating factor macrophage tumor antigen gene therapy.