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Suppression of Type 1 Insulin-like Growth Factor Receptor Expression by Small Interfering RNA Inhibits A549 Human Lung Cancer Cell Invasion in vitro and Metastasis in Xenograft Nude Mice

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Acta Biochimica et Biophysica Sinica 2007年第2期39卷 137-147页

作者： Jianfang QIAN~1 Aiqiang DONG~1 Minjian KONG~1 Zhiyuan MA~2 Junqiang FAN~1 and Guanyu JIANG~3 ~1department of Cardiothoracic Surgery,second affiliated hospital,school of medicine,zhejiang university,hangzhou 310009,china ~2department of Cardiovascular Surgery,Shanghai Jiaotong university affiliated First People's hospital,Shanghai 200080,china ~3department of emergency,second affiliated hospital school of medicine,zhejiang university,hangzhou 310009,china department of Cardiothoracic Surgery Second Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310009China Department of Cardiovascular SurgeryShanghai Jiaotong University Affiliated First People's HospitalShanghai 200080China De

Cancer invasion and metastasis, involving a variety of pathological processes andcytophysiological changes,contribute to the high mortality of lung *** type 1 insulin-like growthfactor receptor (IGF-1R),associated with cancer progression and invasion,is a potential anti-invasion andanti-metastasis target in lung *** inhibit the invasive properties of lung cancer cells,we successfullydown-regulated IGF-1R gene expression in A549 human lung cancer cells by small interfering RNA (siRNA)technology,and evaluated its effects on invasion-related gene expression,tumor cell in vitro invasion,andmetastasis in xenograft nude mice.A549 cells transfected with a plasmid expressing hairpin siRNA forIGF-1R showed a significantly decreased IGF-1R expression at the mRNA level as well as the *** biological assays,transfected A549 cells showed a significant reduction of cell-matrix adhesion,migration and *** with these results,we found that down-regulation of IGR-1Rconcomitantly accompanied by a large reduction in invasion-related gene expressions,including MMP-2,MMP-9,u-PA,and IGF-1R specific downstream *** tail vein injections of plasmid expressinghairpin siRNA for IGF- 1R significantly inhibited the formation of lung metastases in nude *** resultsshowed the therapeutic potential of siRNA as a method for gene therapy in inhibiting lung cancer invasionand metastasis.

关键词： lung cancer invasion metastasis type 1 insulin-like growth factor receptor small interfering RNA

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Changes of phospholipase D activity of rat peritoneal mast cells in degranulation

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Acta Pharmacologica Sinica 2004年第1期 106-111页

作者： Yun- bi LU, Ming WU, Han-liang ZHOUdepartment of Pharmacology, school of medicine, zhejiang university, hangzhou 310031 department of Cardiovascular Thoracic Surgery, second affiliated hospital, school of medicine, zhejiang university, hangzhou 310009, china

IM: To study the changes of phospholipase D (PLD) activity of actively sensitized rat peritoneal mast cells (RPMC) in degranulation. METHODS: Degranulation of RPMC was determined by measurement of β-hexosaminidase release. PLD activity assay was carried out by measurement of PLD product, choline, with chemiluminescent oxidation of luminol. RESULTS: Actively sensitized RPMC challenged with ovalbumin (0.5-8 mg/L for 120 s, 4 mg/L for 15-120 s) resulted in significant activation of PLD accompanied with the increment of P-hexosaminidase release. PLD activity of sensitized RPMC was increased by more than 2-fold compared with that of unsensitized RPMC which contained low levels of PLD activity [(35±13) pmol choline/min in 1×106cells], but β-hexosaminidase releases of the sensitized cells were as low as spontaneous releases.

关键词： ovalbumin phospholipase D immunization mast cells

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What we know about ST13, a co-factor of heat shock protein, or a tumor suppressor?

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Journal of zhejiang university-Science B(Biomedicine & Biotechnology) 2007年第3期8卷 170-176页

作者： SHI Zheng-zheng, ZHANG Jia-wei, ZHENG Shu (The second affiliated hospital, Cancer Institute, school of medicine, zhejiang university, hangzhou 310009, china) The second affiliated hospital Cancer Institute School of Medicine Zhejiang University Hangzhou 310009 China.

This article is to summarize the molecular and functional analysis of the gene “suppression of tumorigenicity 13” (ST13). ST13 is in fact the gene encoding Hsp70 interacting protein (Hip), a co-factor (co-chaperone) of the 70-kDa heat shock proteins (Hsc/Hsp70). By collaborating with other positive co-factors such as Hsp40 and the Hsp70-Hsp90 organizing protein (Hop), or competing with negative co-factors such as Bcl2-associated athanogen 1 (Bag1), Hip facilitates may facilitate the chaperone function of Hsc/Hsp70 in protein folding and repair, and in controlling the activity of regulatory proteins such as steroid receptors and regulators of proliferation or apoptosis. Although the nomenclature of ST13 implies a role in the suppression of tumorigenicity (ST), to date available experimental data are not sufficient to support its role in cancer development, except for the possible down-regulation of ST13 in gastric and colorectal cancers. Further investigation of this gene at the physiological level would benefit our understanding of diseases such as endocrinological disorders, cancer, and neurodegeneration commonly associated with protein misfolding.

关键词： ST13 Hip p48 Hsc/Hsp70 Heat shock protein Protein folding Steroid receptor Tumorigenicity

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Ultrasonographic findings at the resected area after hepatectomy

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Hepatobiliary & Pancreatic Diseases International 2006年第3期5卷 401-405页

作者： Guo-Qiang Mo and Xue-Ming Liu department of Ultrasound, second affiliated hospital, zhejiang university school of medicine, hangzhou 310009, china department of Ultrasound Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009 China.

BACKGROUND: Since hepatectomy has been widely performed, different operative manner, operating areas, and material in the residual cavity may be found ultrasonographi-cally near the resected area after the operation. In this study, we investigated the changes of focal ultrasonography at the resected area post hepatectomy and recognized the characteristic ultrasonographic images. METHODS: 176 patients whose ultrasonographic findings were studied in the residual area during the early and later periods after hepatectomy were retrospectively analyzed in terms of operative manner, operative area, and material in the residual cavity. RESULTS: There were absence of partial hepatic lobe or hepatic segment, focal anechoic area with thin wall or mixed mass at the resected area, and conformation of irregular high-echoic conglomeration at the resected area, cystic non-anechoic area, and mixed mass with irregularly thickened wall at the resected area, inconsistent internal echoes,and color Doppler twinking artifacts around the material and the residual cavity after curettage and aspiration. CONCLUSIONS: Focal ultrasonographic findings at the resected area after hepatectomy vary with different operative procedures, operative area, resection size, absence or existence of material, and kinds of material in the residual cavity.

关键词： ultrasonography liver diseases hepatectomy

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Montelukast modulates lung CysLT1 receptor expression and eosinophilic inflammation in asthmatic mice

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Acta Pharmacologica Sinica 2004年第10期 101-106页

作者： Yan-jun ZHANG, Lei ZHANG, Shao-bin WANG, Hua-hao SHEN, Er-qing WEIdepartment of Pharmacology, zhejiang university school of medicine, hangzhou 310031 zhejiang Provincial Centre for Disease Control and Prevention, hangzhou 310009 department of Respiratory Diseases, The second affiliated hospital, zhejiang university school of medicine, hangzhou 310009, china

AIM: To determine the expressions of cysteinyl leukotriene receptors, CysLT1 and CysLT2, in airway eosinophilic inflammation of OVA-induced asthmatic mice and the modulation by montelukast, a CysLT1 receptor antagonist. METHODS: Asthma model was induced by chronic exposure to ovalbumin (OVA) in C57BL/6 mice. The eosino-phils in bronchoalveolar lavage (BAL) fluid and lung tissues were counted, IL-5 level in BAL fluid was measured, and CysLT1 and CysLT2 receptor mRNA expressions were detected by semi-quantitative RT-PCR. RESULTS: Montelukast (6 mg/kg, once per day for 20 d) significantly suppressed the increased eosinophils in BAL fluid and lung tissue, and increased IL-5 level in BAL fluid in OVA challenged mice. OVA challenge increased CysLT1 but decreased CysLT2 receptor mRNA expression. Montelukast inhibited the increased CysLT1 but not the reduced CysLT2 expression after OVA challenge. CONCLUSION: CysLT receptors are modulated immunologically, and montelukast inhibits up-regulation of CysLT1 receptor

关键词： leukotriene receptors leukotriene antagonists asthma inflammation montelukast

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Induced pluripotent stem cell-related genes influence biological behavior and 5-fluorouracil sensitivity of colorectal cancer cells

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Journal of zhejiang university-Science B(Biomedicine & Biotechnology) 2012年第1期13卷 11-19页

作者： Zhong SHI1,Rui BAI1,Zhi-xuan FU1,Yong-liang ZHU2,Rong-fu WANG3,Shu ZHENG1(1Cancer Institute(Key Laboratory of Cancer Prevention and Intervention,china National Ministry of Education,Key Laboratory of Molecular Biology in Medical Sciences,zhejiang Province,china),the second affiliated hospital,school of medicine,zhejiang university,hangzhou 310009,china)(2department of Gastroenterology,the second affiliated hospital,school of medicine,zhejiang university,hangzhou 310009,china)(3Center for Cell and Gene Therapy,department of Pathology and Immunology,Baylor College of medicine,Houston,Texas 77030,USA) Cancer Institute Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Zhejiang Province China.

Objective:We aimed to perform a preliminary study of the association between induced pluripotent stem cell(iPS)-related genes and biological behavior of human colorectal cancer(CRC) cells,and the potential for developing anti-cancer drugs targeting these ***:We used real-time reverse transcriptase polymerase chain reaction(RT-PCR) to evaluate the transcript levels of iPS-related genes NANOG,OCT4,SOX2,C-MYC and KLF4 in CRC cell lines and cancer stem cells(CSCs)-enriched tumor *** was knockdowned in CRC cell line SW620 by lentiviral transduction.3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT) assays,plate colony formation,and a mouse xenograft model were used to evaluate alterations in biological behavior in NANOG-knockdown SW620 ***,mock-knockdown and NANOG-knockdown cells were treated with 5-fluorouracil(5-FU) and survival rate was measured by MTT assay to evaluate drug ***:A significant difference in the transcript levels of iPS-related genes between tumor spheres and their parental bulky cells was *** knockdown suppressed proliferation,colony formation,and in vivo tumorigenicity but increased the sensitivity to 5-FU of SW620 cells.5-FU treatment greatly inhibited the expression of the major stemness-associated genes NANOG,OCT4,and ***:These results collectively suggest an overlap between iPS-related genes and CSCs in *** a certain gene NANOG may truncate the aggressiveness of CRC cells.

关键词： Induced pluripotent stem cell Cancer stem cell Colorectal cancer NANOG 5-Fluorouracil

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Use of digital subtraction angiography for assessment of digital replantation

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Journal of zhejiang university-Science B(Biomedicine & Biotechnology) 2012年第3期13卷 209-212页

作者： Liu-hong WANG Guang-qiang ZHANG department of Radiology the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Objective: To assess the blood flow of the proper digital artery using digital subtraction angiography (DSA) in the early stage after replantation. Methods: From January 2006 to October 2010, 27 anastomosed arteries in 27 replanted digits were included in the study. The patients included nine males and four females. The patients received DSA at 48 to 96 h after digital replantation. Based on DSA image, the blood flow was classified into normal, slow-running, and flow-stopping types. The patients with normal digital blood flow were given continuous routine treatments; the patients with slow-running flow were given the conservative treatments, such as release of the tight dressings, removal of stitches, keeping warm, the use of massage, and the use of anticoagulants and anti-inflammatory drugs; the patients with flow-stopping received immediate surgical re-exploration. Results: In this series, 23 digits in 11 patients showed a normal blood flow, and these digits all survived. In one of 13 patients, two digits which displayed slow-running flow also survived after conservative treatments. In two of 13 patients, two digits showed flow stopping, with one surviving and one failing after re-exploration and arterial revision. Conclusions: The DSA can be used to assess the blood flow of the proper digital artery in the early stage after replantation. It provides essential information for salvaging the replanted finger.

关键词： Digital subtraction angiography Proper digital artery Replantation Blood flow

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Immunosuppression in Human Peripheral Blood T Lymphocytes by Fluvastatin

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Acta Biochimica et Biophysica Sinica 2004年第10期36卷 649-655页

作者： Li-Hua WU, Yun-Le WAN1, Hai-Yang XIE, Wen-Jin ZHANG, and Shu-Sen ZHENG* Institute of Surgery, The First affiliated hospital, school of medicine, zhejiang university, hangzhou 310003, china 1Centre of organ transplantation, The second affiliated hospital, school of medicine, Zhongshan university, Guangzhou 510000, china Institute of Surgery The First Affiliated Hospital School of Medicine Zhejiang University Centre of organ transplantation The Second Affiliated Hospital School of Medicine Zhongshan University

To investigate the immunosuppressive effect of fluvastatin on the PHA-activated T lymphocytes. T lymphocytes were isolated from the blood of healthy volunteers, cell proliferation and the activation mar- kers expression were examined by flow cytometric analysis. Cytokine secretion was assayed by ELISA. LDH-release assay was used to detect activity of killer cells. NFAT activation was evaluated by TransAMTM ELISA kit. Results were as following. (1) Whereas no modification in CD25 expression was seen, fluvastatin at 5 μM caused a lower level of CD69 expression, accompanied by an essential suppression on proliferation, IL-2 production and cytotoxicity development in PHA-stimulated T cells. However, the level of secreted IL-10 had no change, and the level of IL-4 even experienced a significant increase. (2) Combined with cyclosporine A (CsA), fluvastatin would further repress CD69 expression, cells proliferation and activity of killer cells, meanwhile significantly induced the secretion of IL-4 and IL-10. (3) Fluvastatin treatment also resulted in a strong inhibition of NFAT activation. In conclusion, partly involving the blockage of activation of NFAT, fluvastatin exhibited an immunosuppressive effect in vitro.

关键词： fluvastatin T cell activation T cell proliferation cytokine nuclear factor of activated Tlymphocytes

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Deep lingual arterial chemoembolization of tongue carcinoma with microcapsuled anticancer drug

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Journal of zhejiang university-Science B(Biomedicine & Biotechnology) 2007年第10期8卷 704-708页

作者： HE Hong1, HUANG Jian-qi1, PING Fei-yun1, CHEN Guan-fu1, ZHANG Su-zhan2 (1department of Stomatology, the second affiliated hospital, school of medicine, zhejiang university, hangzhou 310009, china) (2Cancer Institute, the second affiliated hospital, school of medicine, zhejiang university, hangzhou 310009, china) department of Stomatology the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China Cancer Institute the Second Affiliated Hospital School of Medicine Zhejiang University Hangzhou 310009 China

Objective: Microcapsule chemoembolism is a promising treatment of tumors. We describe a deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum. Methods: Lingual artery cast specimens from cadavers were microscopically examined, and 78 patients with tongue cancer were recruited and treated with the deep lingual arterial embolization therapy. Results: Microcapsule embolism occurred approximately at the fifth or sixth level of the deep lingual artery branches. The five-year survival rate was 88.5% (69 out of 78), and the ten-year survival rate 52.6% (41 out of 78). Conclusion: The deep lingual arterial embolization of tongue carcinoma with microcapsuled carboplatinum is an effective therapy to treat carcinoma in mid-margin or mid-body of the tongue.

关键词： Tongue carcinoma Artery cast Arterial chemoembolization Deep lingual arterial embolization Anticancer drug Carboplatinum

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Case Report:Lance-Adams syndrome:a report of two cases

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Journal of zhejiang university-Science B(Biomedicine & Biotechnology) 2007年第10期8卷 715-720页

作者： ZHANG Yan-xing1,2, LIU Jian-ren1, JIANG biao3, LIU Hui-qin1, DING Mei-ping1, SONG Shui-jiang1, ZHANG Bao-rong1, ZHANG Hong4, XU Bin5, CHEN Huai-hong6, WANG Zhong-jin1, HUANG Jian-zheng1 (1department of Neurology, the second affiliated hospital, school of medicine, zhejiang university, hangzhou 310009, china) (2department of Neurology, Shaoxing People’s hospital, Shaoxing 312000, china) (3department of Radiology, the second affiliated hospital, school of medicine, zhejiang university, hangzhou 310009, china) (4department of Nuclear medicine, the second affiliated hospital, school of medicine, zhejiang university, hangzhou 310009, china) (5department of Neurology, the second affiliated hospital, zhejiang university of Traditional Chinese medicine, hangzhou 310005, china) (6department of Geratology, the second affiliated hospital, school of medicine, zhejiang university, hangzhou 310009, china) department of Neurology the Second Affiliated Hospital School of Medicine Zhejiang University department of Neurology Shaoxing People’s Hospital department of Radiology the Second Affiliated Hospital School of Medicine Zhejiang University

Chronic post-hypoxic myoclonus, also known as Lance-Adams syndrome (LAS), is a rare complication of successful cardiopulmanry resuscitation often accompanied by action myoclonus and cerebellar ataxia. It is seen in patients who have un-dergone a cardiorespiratory arrest, regained consciousness afterwards, and then developed myoclonus days or weeks after the event. Worldwide, 122 cases have been reported in the literature so far, including 1 case of Chinese. Here we report 2 Chinese LAS patients with detailed neuroimagings. Cranial single photon emission computed tomography (SPECT) of patient 1, a 52-year-old woman, showed a mild hypoperfusion in her left temporal lobe, whereas patient 2, a 54-year-old woman, manifested a mild bilateral decrease of glucose metabolism in the frontal lobes and a mild to moderate decrease of the N-acetyl aspartate (NAA) peak in the bilateral hippocampi by cranial [18F]-fluorodeoxyglucose positron emission tomographic (PET) scan and cranial magnetic resonance spectroscopy (MRS), respectively. We also review the literature on the neuroimaging, pathogenesis, and treatment of LAS.

关键词： Lance-Adams syndrome Chronic post-hypoxic myoclonus Action myoclonus Cerebellar ataxia Single photon emission computed tomography Positron emission tomography Magnetic resonance spectroscopy

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