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中国科学B辑(英文版) 1988年第6期31卷 719-725页

作者：高进 Department of pathology institute of Basic Medical Sciences Chinese Academy of Medical Sciences. Beijing

For the study of invasion of tumor cells in vitro and in vivo methods were used to observe theinvasion process and morphological characteristics of tumor cells. The different animal tumor cells andcell lines from human tumors were used. The process of cancer cells in vitro invasion can be dividedinto 5 stages. We suggest that filopodia protruding from the tumor cell margin seem to play an im-portant role in the initiation of cell invasion. For experimental study of cancer metastasis we established three spontaneous metastatic models, in-cluding spontaneous lymphatic and hematogenous metastasis of mouse uterine cervix carcinoma No 14(U14)and No 27(U27), and third spontaneous lung metastasis in mouse forestomach carcinoma （FC）. Two tumorcell lines are established: One is MFC cell line which is derived from FC tumor; second cell line isMUCC which is derived from the U27 tumor. These metastasis models and their cell lines are veryuseful for studying the mechanism of metastasis, tumor heterogenicity an

关键词： metastasis invasion lymphatic uterine cervix metastatic spontaneous morphological hepatoma initiation

GEMFIBROZIL　INDUCED　MYOSITIS：A　CASE　REPORT　WITH　LIGHT　MICROSCOPIC　AND　ULTRASTRUCTURAL　STUDY

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Chinese Medical Sciences Journal 1994年第2期9卷 129-131页

作者： $$$$Louis Tsun-cheung Chow MRCPath FRCPA FACA and Wing-hing Chow MRCP (institute of pathology,Queen Elizabeth Hospital,Hong Kong ) institute of pathology Queen Elizabeth Hospital Hong Kong.

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ＧＥＭＦＩＢＲＯＺＩＬＩＮＤＵＣＥＤＭＹＯＳＩＴＩＳ：ＡＣＡＳＥＲＥＰＯＲＴＷＩＴＨＬＩＧＨＴＭＩＣＲＯＳＣＯＰＩＣＡＮＤＵＬＴＲＡＳＴＲＵＣＴＵＲＡＬＳＴＵＤＹ￥ＬｏｕｉｓＴｓｕｎ－ｃｈｅｕｎｇＣｈｏｗ；ＭＲＣＰａｔｈ；ＦＲＣＰＡ；ＦＡＣＡａｎｄＷ...

关键词： gemfibrozil 肌肉综合症药物治疗药物不良反应肌炎

Safety of Human Recombinant Proteins

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Biomedical and Environmental Sciences 1997年第1期10卷 65-71页

作者： BERNHARD RYFFEL (institute of pathology, University of Basel, CH-4031 Basel , Switzerland) ( Department of Immunology, Medical School Observatory 7925, University of Cape Town,South Africa.) institute of pathology University of Basel Switzerland.

Recombinant human proteins play an important role in therapy, especially in stimulating the hematopoiesis after chemotherapy, e. g., erythropoietin and colony stimulating factors,while several promising candidates such as IL-6, IL-12, thrombopoietin and others are in clinical development. Since the recombinant proteins are copies of endogenous proteins, it was assumed that they would be well tolerated. While this assumption is correct for some, other proteins proved to be less well tolerated. Therefore, preclinical safety assessment of these pro teins is necessary. Based on the experience with several proteins, some guidance for the safety assessment can be given. Furthermore, data are presented demonstrating that preclinical toxi city studies may have a predictive value for man. Limitations of the classical approach of safety tests and new concepts are discussed

关键词： Rev Safety of Human Recombinant Proteins

The effect of lipopolysaccharides on the expression of CD14 and TLR4 in rat Kupffer cells

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Hepatobiliary & Pancreatic Diseases International 2003年第2期2卷 581-585页

作者： Jun-Ming Feng Jing-Quan Shi You-Sheng Liu the Research institute of pathology Southwestern Hospital, Third Military Medical University, Chongqing 400038, China Research institute of pathology Southwestern Hospital Third Military Medical University Chongqing 400038 China. fjmds@***

OBJECTIVE: To assess the effect of lipopolysaccharides (LPS) on the expression of CD14 and TLR4 in rat Kupffer cells (KCs). METHODS: In rat KCs induced by LPS, the changes of CD14 and TLR4 expression were measured by RT-PCR and immunohistochemistry, and the expressions of TNF-αmRNA, IL-6mRNA or the concentrations of TNF-α, IL-6 were estimated by in situ hybridization, radioimmunoassay, and others. RESULTS: The expressions of CD14 and TLR4 in KCs induced by LPS were markedly increased in a dose-dependent manner (10 mg/L-1μg/L) or in a time-dependent manner (0.5 h-24 h), with the peaked expression of CD14 at 3-6 hours. The expressions of CD14 and TLR4 in KCs stimulated by the active mediators from KCs which had been exposed to LPS for 1 hour were obviously increased. CONCLUSIONS: There is a close relationship between LPS or the active mediators from KCs induced by LPS and the expressions of CD14, TLR4. It is implied that the increase of TLR4, CD14 expression may be induced by LPS within 1--3 hours, and further increase of TLR4, CD14 expression may be correlated with the cytokines produced bv KCs.

关键词： lipopolysaccharides Toll-like receptor TNF interleukin mediator cytokines Kupffer cell

Effect of Repetitive Bleeding on NADH-Cytochrome b_5 Methemoglobin Reductase Activity and Molybdenum Content in Erythrocytes of Rats

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Biomedical and Environmental Sciences 1996年第4期9卷 393-398页

作者： YANG YUAN WANG FAN Li GUANG-SHENG AND KANG DE-REN (Gastroenterological Center, Hospital No. 222, People,s Liberation Army,Jilin 132011, China Department of pathology, institute of Preclinical Science, Norman Bethune University of Medical Sciences,Ch Gastroenterological Center Hospital No. 222 People's Liberation Army Jilin China.

Reticulocytosls in rats was induced by repetitive bleeding. Both the in vitro and the in vivo studies showed that the detected reductive speed of methemoglobin of the bleeding group was faster than that of the control group at all time intervals. At the same time, the NADH-cytochrome b5 methemoglobin reductase activity and the molybdenum content in erythrocytes of the bleeding group were significantly increased. Regressional analysis showed that there was a significantly positive correlation between the enzyme activity and the molybdenum content. It is proposed that molybdenum might be required for the enzyme activity

关键词： Activity NADH Effect of Repetitive Bleeding on NADH-Cytochrome b5 Methemoglobin Reductase Activity and Molybdenum Content in Erythrocytes of Rats

Differential expression of autocrine motility factor receptor (AMFR) mRNA in normal and cancer cells detected by in situ hybridization

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Cell Research 1995年第2期5卷 221-234页

作者： HUANG BAIQU AVRAHAM RAZ(institute of GEnetics and Cytology, NOrtheast Normal University, Changchun 130024, China.)(The Karmanos Cancer institute, Department of pathology and Radiationn Oncology, Wayne State University Medical School, Detroit, MI 48201, U institute of Genetics and Cytology Northeast Normal University Changchun China Department of pathology and Radiationn Oncology The Karmanos Cancer Institute Wayne State University Medical School Detroit USA

The receptor for autocrine motility factor (AMFR) is known to be involved in the process of AMF-mediated cell migration and metastasis. This paper describes the procedures of non-radioactive in situ hybridization (ISH) detection of AMFR mRNA in both paraffin-embedded surgical sections and cultured cells using either biotinylated oligonucleotide probes or digoxigenin-labeled RNA probes. The results showed that the AMFR mRNA was expressed at an enhanced level in hyperplaJstic and malignant tissues of breast and prostate cancer patient surgical specimens, indicating that the elevated AMFR expression was associated with the tissue malignancy Moreover, AMFR mRNA was detected in both normal and earcinoma cells when cultured at a subconfluent density. However, AMFR expression was inhibited in confluent normal (3T3-A31 murine fibroblast and FHs738BL human bladder) cells while it continued to express in carcinoma (J82 human bladder)and metastatic (3T3-M murine fibroblast) cells irrespective of cell density This suggested a cell-cell contact downregulation of AMFR mRNA expression in normal but not in cancer cells. The ISH data obtained in this study are closely consistent with the AMFR protein expression pattern previously reported, implying that the differential expression of AMFR gene may be regulated and controlled at the transcriptional level.

关键词： Autocrine motility factor receptor (AMFR) non-radioactive in situ hybridization biotinylated probe digoxigenin-labeled RNA probe

Preparation of monoclonal antibody against apoptosis-associated antigens of hepatoma cells by subtractive immunization

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World Journal of Gastroenterology 2002年第5期8卷 808-814页

作者： Lian-Jun Yang Wen-Liang Wang Department of pathology,institute of Cancer Research,The Fourth Military Medical University (FMMU),Xian 710032,Shaanxi Province,China Department of pathology Institute of Cancer Research The Fourth Military Medical University Xi'an 710032 Shaanxi Province China.

AIM: To elucidate the expression of the apoptosis-associatedmolecules in human primary hepatocellular carcinoma (HCC)cells, and prepare the monoclonal antibodies (mAb) againstthe apoptosis-associated antigens of HCC ***: Human HCC cell line HCC-9204 cells wereinduced apoptosis with 60 mL.L-1 ethanol for 6 h and theirmorphological changes were observed by transmissionelectron microscope. The cell DNA fragmentations weredetected by Terminal Deoxynucleotidyl transferase-mediateddUTP nick end labeling (TUNEL) assay, and the cell DNAcontents by flow cytometry. Ten mice were immunized withethanol-induced apoptotic HCC-9204 cells with the methodof subtractive immunization, while the other 10 mice usedas the control were immunized by the routine *** tail blood of all the mice were prepared after the lastimmunization, and the produced antibodies were determinedby the immunocytochemical ABC staining. The splenic cellsof the mice whose tail blood sera-HCC-9204 cells serumreactions were most different between the apoptotic andthe non-apoptotic were prepared and fused with the mousemyeloma cell line SP2/0 cells. The positive antibodies wereselected by ELISA assay. The fusion rates of hybridoma cellsand the producing rates of antibodies were calculated. Thefused cells that secreted candidate objective antibody werecloned continually with the of limited dilution method, andthen selected and analyzed further by theimmunocytochemical ABC staining. The chromosomes of thecloned hybridoma cells that secreted objective mAb and themAb immunoglobulin (Ig) subtype of the prepared mAb werealso determined. The molecular mass of the mAb associatedantigen was analyzed by Western blot ***: HCC-9204 cells treated with 60 mL.L-1 ethanolfor 6 h, manifested obvious apoptotic morphological changes,the majority of the cells were TUNEL-positive, and the sub-G1 apoptotic peak was evident. There were 2 mice in theexperimental group whose tail blood serum reacted stronglywi

关键词：肝癌单克隆抗体免疫抑制细胞凋亡相关抗原

AICAR inhibits proliferation and induced S-phase arrest,and promotes apoptosis in CaSki cells

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Acta Pharmacologica Sinica 2007年第12期28卷 1984-1990页

作者： Tong-ju GUAN~2,Feng-jin QIN~3,Jian-hai DU~4,Li Geng~3,You-yi ZHANG~(4,5),Min LI~(2,5)~2 institute of pathology,The School of Basic Medicine,Lanzhou University,Lanzhou 730000,China ~3 Department of Gynaecology andObstetrics,Peking University Third Hospital,Beijing 100083,China ~4 institute of Vascular Medicine,Peking University Third Hospital andKey Laboratory of Molecular Cardiovascular Sciences Ministry of Education,Beijing 100083,China institute of pathology The School of Basic Medicine Lanzhou University Lanzhou China Department of Gynaecology and Obstetrics Peking University Third Hospital Beijing China institute of Vascular Medicine Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Beijing China

Aim:The aim of the present study was to determine the effect of 5-aminoimidazole-4-carboxamide-ribonucleoside （AICAR） on proliferation,cell cycle,and apoptosisin the human epithelial cervical cancer cell line CaSki ***:Cell countand 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide assay were usedto determine cell proliferation and *** 33258 staining was con-ducted to distinguish the apoptotic *** cycle and Annexin-V/propidiumiodide staining were analyzed by fluorescence-activated cell sorting （FACS）.AWestern blot assay was used to evaluate the expression of AKT （also known asprotein kinase B）,mammalian target of rapamycin （mTOR）,p53,and extracellularsignal-regulated kinase （ERK）.Results:AICAR （500 μmol/L） significantly inhibi-ted the proliferation of CaSki cells treated for 24,48,and 72 h as determined by *** cells at the G1and G2phases were dramatically decreased while cells atthe S phase were increased in response to AICAR treatment for 24,48,and 72 *** MTT assay showed less viable cells and Hoechst fluorescent staining showedmore apoptotic cells upon AICAR *** results of the Annexin-Vstaining demonstrated a time-dependent increase of apoptosis in cells treatedwith AICAR for 24,36,and 48 ***,AICAR activated caspase-3 in atime-dependent *** was also found that AICAR inhibited the phosphory-lation of AKT and mTOR,which are important kinases regulating cell growth *** stimulation obviously increased the expression of the tumorsuppressor p53 and the phosphorylation of ***:AICAR inhibitedproliferation and induced S phase arrest and promoted apoptosis in CaSki cells,which might be mediated by the downregulation of the AKT/mTOR pathway andthe upregulation of the p53/ERK pathway.

关键词： AICAR proliferation apoptosis CaSki cells

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昆虫病原细菌“010”的鉴定

昆虫学报 1973年第1期16卷 91-93页

作者： SECTION OF INSECT pathology(institute of Zoology, Academia Sinica) 昆虫病理组中国科学院动物研究所

1970年初,我们发现从蜜蜂幼虫中分离的芽孢杆菌“010”在生产性能和对昆虫的致病方面,均显示了良好的特性。该年我组曾与南苑公社化工厂共同对此菌的生产及毒效进行了初步摸索。继之,考察了它的营养要求及某些生产工艺条件,并对不同害... 详细信息

1970年初,我们发现从蜜蜂幼虫中分离的芽孢杆菌“010”在生产性能和对昆虫的致病方面,均显示了良好的特性。该年我组曾与南苑公社化工厂共同对此菌的生产及毒效进行了初步摸索。继之,考察了它的营养要求及某些生产工艺条件,并对不同害虫进行了室内及大田的毒力测定。1971—1972年,通过培养基试验和上罐考察,选出两组综合利用较为理想的培养基。其中一组配比是:豆饼粉2.4％、玉米浆2％、麦芽粉4％、碳酸钙0.1％。菌数曾达48亿/毫升。“010”杀虫范

关键词：毒效病原细菌敏感性测定蜜蜂幼虫豆饼粉凝集试验吸附试验毒力测定血清学试验试验结果

Local Proinflammatory Effects of Repeated Skin Exposure to Warfarin, An Anticoagulant Rodenticide in Rats

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Biomedical and Environmental Sciences 2011年第2期24卷 180-189页

作者： Aleksandra POPOV Ivana MIRKOV Lidija ZOLOTAREVSKI Milena JOVIC Sandra BELIJ Dragan KATARANOVSKI Milena KATARANOVSKI Department of Ecology Institute for Biological Research "Sinisa Stankovic" University of Belgrade institute for pathology Military Medical Academy institute of Zoology Faculty of Biology University of Belgrade institute of Physiology and Biochemistry Faculty of Biology University of Belgrade

Objective： To evaluate the effects of epicutaneous application of anticoagulant warfarin, by examining the presence of tissue injury and immune/inflammatory activity in exposed skin. Methods： Rats were exposed to warfarin by applying 10 μg of warfarin‐sodium to 10‐12 cm 2 skin （range 0.8‐1 μg per 1 cm 2 ） for 3 consecutive days. Tissue injury was evaluated by lipid peroxidation, histomorphological changes and signs of reparative activity in skin. T cell infiltration and selected aspects of epidermal cell activity were examined as indicators of immune/inflammatory skin response to warfarin application. Results： Repeated warfarin application exerted no effect on skin metabolic viability, but resulted in tissue injury （increased malondialdehyde, MDA, production, evident histo‐morphological changes in epidermis and dermis depicting cell injury and death）. Increased numbers of proliferating cell nuclear antigen （PCNA ＋） cells indicated reparative processes in injured skin. Infiltration of CD3 ＋ cells （T lymphocytes） along with the increased production of tumor necrosis factor‐α （TNF‐α） by epidermal cells from warfarin‐treated skin and their co‐stimulatory effect in an in vitro T‐cell activation assay demonstrated immunomodulatory effects of epicutaneous warfarin. Conclusion： Presented data have documented tissue damage associated with immune/ inflammatory activity in skin exposed to warfarin. Observed effects are relevant to immunotoxic potential of this anticoagulant in settings of external exposure.

关键词： Rats Warfarin Epicutaneous exposure Tissue damage Skin inflammation