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Cell Research 2004年第6期14卷 497-506页

作者： Li ZHENG, Jia Qiang REN, Hua LI, Zhao Lu KONG, Hong Guang ZHU department of Pathology, shanghai medical college, fudan university, shanghai, 2.0032, china. Institute of Irradiation Medicine, fudan university, shanghai, 2.0032, china department of Pathology shanghai medical college fudan university Shanghai 200032 China

Overexpression and activation of HER-2/neu (also known as c-erbB-2), a proto-oncogene, was found in about 30% of human breast cancers, promoting cancer growth and making cancer cells resistant to chemo- and radio-therapy. Wild-type p53 is crucial in regulating cell growth and apoptosis and is found to be mutated or deleted in 60-70% of human cancers. And some cancers with a wild-type p53 do not have normal p53 function, suggesting that it is implicated in a complex process regulated by many factors. In the present study, we showed that the overexpression of HER-2/neu could decrease the amount of wild-type p53 protein via activating PI3K pathway, as well as inducing MDM2 nuclear translocation in MCF7 human breast cancer cells. Blockage of PI3K pathway with its specific inhibitor LY294002 caused Gl-S phase arrest, decreased cell growth rate and increased chemo- and radio-therapeutic sensitivity in MCF7 cells expressing wild-type p53. However, it did not increase the sensitivity to adriamycin in MDA-MB-453

关键词： HER-2/neu PI3K breast cancer p53 MDM2

Lymphangiogenic and angiogenic microvessel density in human primary sporadic colorectal carcinoma

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World Journal of Gastroenterology 2008年第1期14卷 101-107页

作者： Ge Yan, Xiao-Yan Zhou, San-Jun Cai, Gui-Hong Zhang, Jun-Jie Peng, Xiang Du, department of Pathology, Cancer Hospital of fudan university department of oncology, shanghai medical college, fudan university Colorectal Cancer Center, fudan university, 270 Dong’an Road, shanghai 2.0032, china department of Pathology Cancer Hospital of Fudan University Shanghai 200032 China. dx2008cn@***

AIM： To investigate the distribution pattern of lymphatic vessels and microvessels in sporadic colorectal carcinoma （SCRC） and their relationship to metastasis and prognosis. METHODS： The lymphatic vessel density （LVD） and microvessel density （MVD） in tumor tissue obtained from 132 patients with primary SCRC, including 74 with metastases and 58 without metastases, were evaluated by immunohistochemistry using antibodies directed against D2-40 and yon Willebrand factor （vWF）. RESULTS：（1） The lymphatic vessels and microvessels at central portions of SCRC often had a reticular architecture with numerous tiny and ill-defined lumina, while those at tumor borders had large and open lumina. The LVD and MVD were both obviously higher in colorectal cancer patients with metastases than in those without （P 〈 0.001）. （2） For each one lymphatic vessel increased, there was a 1.45-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of LVD in predicting metastasis or non-metastasis in SCRC were 71.62% and 56.90%, respectively, and the corresponding LVD was 5. For each one microvessel increased, there was a 1.11-fold increase in the risk of metastasis in SCRC. The specificity and sensitivity of MVD were 66.22% and 51.72%, respectively. （3） Double labeling immunohistochemistry showed D2-40 immunoreactivity to be specific for lymphatic vessels. （4） Univariate analysis indicated that high LVD, high MVD, as well as co-accounting of high LVD and high MVD were associated with patient＇s poor disease-free survival （Puni 〈 0.05）; multivariate analysis indicated that co-accounting of LVD and MVD was an independent prognostic factor of colorectal cancer, CONCLUSION： D2-40 is a new specific antibody for lymphatic endothelial cells. Lymphogenesis and angiogenesis are commonly seen in SCRC, especially at tumor borders. The detection of LVD and MVD at tumor borders may be useful in predicting metastasis and prognosis in patients with SCRC, and, in particular, coaccount

关键词： Lymphangiogenesis Angiogenesis Lymphaticvessel density Microvessel density Sporadic colorectalcarcinoma Metastasis

Germline mutation analysis of hPMS2 gene in Chinese families with hereditary nonpolyposis colorectal cancer

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World Journal of Gastroenterology 2010年第30期16卷 3847-3852页

作者： Xia Sheng, Xiao-Yan Zhou, Xiang Du, Tai-Ming Zhang, WeiQi Sheng, Da-Ren Shi, department of Pathology, shanghai Cancer Center, fudan university, shanghai 2.0032, china department of oncology, shanghai medical college, fudan university, shanghai 2.0032, china Heng-Hua Zhou, department of Pathology, shanghai Ninth People’s Hospital Affi liated to shanghai Jiao Tong university School of Medicine, shanghai 200011, china San-Jun Cai, department of Abdominal Surgery, Cancer Center, fudan university, shanghai 2.0032, china department of Pathology Shanghai Cancer Center Fudan University 270 Dong An Road Shanghai 200032 China. shengweiqi2006@***

AIM: To study the germline mutation of hPMS2 gene in 26 unrelated Chinese hereditary nonpolyposis colorectal cancer (HNPCC) probands and to fulfill the screening strategy for HNPCC in Chinese. METHODS: Genomic DNA was extracted from the peripheral blood. To avoid the interference of pseudogene in detection of the remaining 11 exons (exon 1-5, 9, 11-15), long-range polymerase chain reaction (PCR) was conducted to amplify the complete coding region of hPMS2 gene firstly. Then 1/8 of the PCR productswere used as template to amplify the individual exon respectively and DNA sequencing was done. Direct DNA sequencing of the conventional PCR products of exon 6, 7, 8 and 10 of hPMS2 gene was performed. The same analysis was made in 130 healthy persons without family histories of HNPCC to further investigate the pathological effects of the detected missense mutation. RESULTS: One HNPCC proband fulf illed Bethesda guidelines and was found to carry the germline mutation of hPMS2 gene, which has not been reported in Chinese HNPCC families. It was a missense mutation at c.1532C>T of exon 11. It was detected in three controls as well with an occurrence rate of 2.3% (3/130). Since it could not be found in the PMS2-single nucleotide polymorphism (SNP) database, this missense mutation is a new SNP unreported up to date. Meanwhile, 260 reported SNPs of hPMS2 gene were detected in the 26 HNPCC probands. The 2nd and 5th exons were probably the hot SNP regions of hPMS2 gene in Chinese HNPCC families involving 53.1% of all reported SNP. CONCLUSION: The germline mutation of hPMS2 gene may be rare in Chinese HNPCC families. The 2nd and 5th exons are hot SNP regions of hPMS2 gene.

关键词： Hereditary nonpolyposis colorectal cancer hPMS2 Missense mutation Single nucleotide polymorphism Colorectal cancer

On the generalized Busemann-Petty problem

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Science china Mathematics 2007年第8期50卷 1103-1116页

作者： Song-jun L~(1,2+) Gang-song LENG~1 1.college of Mathematics and Computer Science,Chongqing Normal university,Chongqin 400047,china 2.department of Mathematics,shanghai university,shanghai 200444,china college of Mathematics Computer Science Chongqing Normal University Chongqin 400047 China department of Mathematics Shanghai University Shanghai 200444 China

The generalized Busemann-Petty problem asks whether the origin-symmetric convex bodies in ? n with a larger volume of all i-dimensional sections necessarily have a larger volume. As proved by Bourgain and Zhang, the answer to this question is negative if i > 3. The problem is still open for i = 2, 3. In this article we prove two specific affirmative answers to the generalized Busemann-Petty problem if the body with a smaller i-dimensional volume belongs to given classes. Our results generalize Zhang’s specific affirmative answer to the generalized Busemann-Petty problem.

关键词： star body cross i-section dual mixed volume Radon transform 52A30 52A40

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Antisense Tiam1 Down-Regulates the Invasiveness of 95D Cells in Vitro

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Acta Biochimica et Biophysica Sinica 2004年第8期36卷 537-540页

作者： Min HOU, Li TAN, Xia WANG, and Yun-Song ZHU department of Molecular Genetics, shanghai medical college, fudan university & Key Laboratory of Molecular Medicine, Ministry of National Education, shanghai 2.0032, china department of Molecular Genetics Shanghai Medical College Fudan University & Key Laboratory of Molecular Medicine Ministry of National Education

As a specific guanine nucleotide exchange factor of Rac1, Tiam1 (T-lymphoma invasion and metastasis inducing protein 1) is involved in a number of cellular events, such as cytoskeleton reorganization, cell adhesion, and cell migration. Since Tiam1 was implicated in the invasion and metastasis of T-lymphoma cells and breast tumor cells, we compared the expression level of Tiam1 in two human giant-cell lung carcinoma cell strains with high or low metastasis potential, and found that Tiam1 expression level in high-metastatic 95D cells was higher than that in low-metastatic 95C cells. To further confirm the role of Tiam1 in invasion and metastasis, we constructed the antisense Tiam1 expression plasmid (pcDNA3-anti- Tiam1), which was transfected into 95D cells. A stable transfected clone with decreased Tiam1 expression was screened and selected for further research. Transwell assay showed that down-regulation of endogenous Tiam1 by anti-Tiam1 can reduce the in vitro invasiveness of 95D cells. Our results suggested that Tiam1 signaling contributed to the invasion and metastasis of the human giant-cell lung carcinoma cells.

关键词： T-lymphoma invasion and metastasis inducing protein 1 (Tiam1) invasion and metastasis

Effects of paclitaxel on proliferation and apoptosis in human acute myeloid leukemia HL-60 cells

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Acta Pharmacologica Sinica 2004年第3期25卷 124-130页

作者： Yun-feng WAN,Xue-qing GUO1,Zheng-hua WANG ,Kang YING1,Ming-hui YAO2 1 department of Pharmacology,shanghai medical college,fudan university,shanghai 2.0032 1United Gene Scientific Technology Company,shanghai 200092,china department of Pharmacology Shanghai Medical College Fudan University United Gene Scientific Technology Company Shanghai 200092 China

AIM: To investigate the regulatory effect of paclitaxel on proliferation and apoptosis in human acute leukemia HL- 60 cells. METHODS: HL-60 cell growth was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tertrazolium bromide (MTT) colorimetric assay. Cell cycle kinetics and apoptosis were analyzed by flow cytometry and micro- scopic examination. In addition, DNA microarrays containing 14400 EST elements were used to investigate the gene expression pattern of HL-60 cells exposed to paclitaxel 1 μmol/L. RESULTS: Paclitaxel inhibited HL-60 cell growth significantly in a dose-dependent and time-dependent manner (P2/M phase and multinucleated cells were also observed after treatment with paclitaxel 0.1 and 1 μmol/L. Among 14400 EST elements, 277 genes were found to be markedly up- or down-expressed in the HL-60 cells treated with paclitaxel 1 μmol/L for 0.5 h, comprising 210 known genes and 67 unknown genes. CONCLUSION: Paclitaxel suppresses the growth of HL-60 cells in vitro by causing cell-cycle arrest and apoptosis. The results of microarray suggest that paclitaxel initiates apoptosis through multiple mechanisms.

关键词： acute promyelocytic leukemia paclitaxel cultured tumor cells genes apoptosis oligonucleotide array sequence analysis cell cycle HL-60 cells

Regularity of harmonic maps with the potential

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Science china Mathematics 2006年第5期49卷 599-610页

作者： CHU Yuming & LIU Xiangao department of Mathematics, Huzhou Teachers college, Huzhou 313000, china Institute of Mathematics, fudan university, shanghai 200433, china department of Mathematics Huzhou Teachers College Huzhou 313000 China Institute of Mathematics Fudan University Shanghai 200433 China

The aim of this work is to prove the partial regularity of the harmonic maps with potential. The main difficulty caused by the potential is how to find the equation satisfied by the scaling function. Under the assumption on the potential we can obtain the equation, however, for a general potential, even if it is smooth, the partial regularity is still open.

关键词： harmonic map, partial regularity, potential.

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The Mystery of Sleep:Molecular Mechanisms of Histaminergic Roles in Sleep-wake Regulation

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生物物理学报 2009年第S1期25卷 52-53页

作者： Zhi-Li Huang1,2,Wei-Min Qu2 1 State Key Laboratory of medical Neurobiology 2.department of Pharmacology, shanghai medical college of fudan university, shanghai 2.0032, china.

The histaminergic neurons are confined to the tuberomammillary nucleus (TMN) of the posterior hypothalamus, and send their fibers to almost all regions of the brain. A

关键词： TMN

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Crosstalk between tumor cells and microenvironment via Wnt pathway in colorectal cancer dissemination

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World Journal of Gastroenterology 2008年第12期14卷 1823-1827页

作者： Dan Huang, Xiang Du, department of Pathology, Cancer Hospital of fudan university department of oncology, shanghai medical college, fudan university, shanghai 2.0032, china 270 Dong An Road Department of Pathology Cancer Hospital Fudan University Shanghai 200032 China. dx2008cn@***

Invasion and metastasis are the deadly face of malignant tumors. Considering the high rate of incidence and mortality of colorectal cancer, it is critical to determine the mechanisms of its dissemination. In the parallel investigation of the invasive front and tumor center area of colorectal cancer (CRC), observation of heterogeneous β-catenin distribution and epithelial-mesenchymal transition (EMT) at the invasive front suggested that there might be a crosstalk between tumor cells and the tumor microenvironment. Wnt signaling pathway is also involved in the cancer progression due to its key role in CRC tumorigenesis. Moreover, in recent years, there is increasing evidence that the regulators of microenvironment, including extracellular matrix, growth factors and inflammatory factors, are associated with the activation of Wnt pathway and the mobility of tumor cells. In this review, we will try to explain how these molecules trigger metastasis via the Wnt pathway.

关键词： Invasion Microenvironment Colorectalcancer Epithelial-mesenchymal transition Wnt β-catenin

Transcriptional Regulation of Urokinase Receptor in High-(95D) and Low-metastatic (95C) Human Lung Cancer Cells

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Acta Biochimica et Biophysica Sinica 2004年第6期36卷 405-411页

作者： Chun-Yang LI, Li TAN, Guo-Jing ZHANG, Ping LI, Chang TONG, Jing FAN, and Yun-Song ZHU* Key Laboratory, the Education Ministry, department of Biochemistry and Molecular Biology, shanghai medical college,fudan university, shanghai 2.0032, china Key Laboratory the Education Ministry Department of Biochemistry and Molecular Biology Shanghai Medical College Fudan UniversityShanghai 200032 China

To study the transcriptional regulation of urokinase receptor (uPAR) in high- (95D) and low-metastatic (95C) human lung cancer cells, we performed PCR to amplify 2238 bp uPAR promoter from 95C and 95D cells. According to the results of sequencing, five different bases are found in uPAR promoter between 95C and 95D cells. The results of luciferase activity assay showed that these differences have no significant effect on the uPAR promoter activity. Based on a normal uPAR promoter, progressive truncated mutants were constructed. The transient transfection/reporter assay showed that the promoter region from –136 to +9 may interact with relevant nuclear factors, which result in different levels of uPAR expression between 95C and 95D cells.

关键词： uPAR promoter transcriptional regulation