Zhao Zhou | Wageningen University and Research Centre (original) (raw)
Papers by Zhao Zhou
GPIIb/IIIa and ␣v3. We used chimeric (c) 7E3 Fab (ReoPro) and murine (m) 7E3 F(ab) 2 to elucidat... more GPIIb/IIIa and ␣v3. We used chimeric (c) 7E3 Fab (ReoPro) and murine (m) 7E3 F(ab) 2 to elucidate the role of these integrins in angiogenesis, tumor growth, and metastasis. These antibodies are potent inhibitors of GPIIb/IIIa and ␣v3. c7E3 Fab inhibited ␣v3-mediated human umbilical vein endothelial (HUVEC) and melanoma cell adhesion, migration, invasion, and basic fibroblast growth factor stimulated proliferation of HUVECs (IC 50 values range from 0.15 to 5 g/ml for different assays). In an in vitro angiogenesis assay, c7E3 Fab inhibited basic fibroblast growth factor and platelet-stimulated capillary formation of HUVECs (IC 50 ؍ 10 g/ml and 15 g/ml, respectively), demonstrating that endothelial ␣v3 is important for sprouting, and platelet-stimulated sprouting is mediated by GPIIb/IIIa. In an experimental metastasis assay, a single pretreatment of human melanoma cells with c7E3 Fab (2.5 g/ml) inhibited lung colonization of the tumor cells in severe combined immunodeficient mice. In vivo, m7E3 F(ab) 2 partially inhibited growth of human melanoma tumors in nude mice compared with control-treated animals. These data suggest that tumor cell-expressed integrins are important but not the only component involved in tumor growth. Because c7E3 Fab and m7E3 F(ab) 2 do not cross-react with murine integrins, this inhibition of metastasis and tumor growth is attributable to direct blockade of human tumor ␣v3 integrins. m7E3 F(ab) 2 completely blocked tumor formation and growth of human melanoma tumors growing in nude rats. In this xenograft model, m7E3 F(ab) 2 simultaneously binds to both human tumor and host platelet GPIIb/IIIa and endothelial ␣v3 integrins, thus participating as an antiangiogenic and an antitumor agent. Collectively, these results indicate that combined blockade of GPIIb/IIIa and ␣v3 affords significant antiangiogenic and antitumor benefit.
International Journal of Cancer, 2004
Integrins of the αv family, such as αvβ3 and αvβ5, are implicated in tumor-induced angiogenesis; ... more Integrins of the αv family, such as αvβ3 and αvβ5, are implicated in tumor-induced angiogenesis; but their role in tumor growth has not been fully explored. CNTO 95 is a fully human antibody that recognizes the αv family of integrins and is likely to be less immunogenic in humans compared to chimeric or humanized antibodies. CNTO 95 bound to purified αvβ3 and αvβ5 with a Kd of approximately 200 pM and to αv integrin–expressing human cells with a Kd of 1–24 nM. In vitro, CNTO 95 inhibited human melanoma cell adhesion, migration and invasion at doses ranging 7–20 nM. In a rat aortic ring sprouting assay, CNTO 95 (approx. 70 nM) completely inhibited sprouting. Using a human melanoma xenograft model in nude mice wherein CNTO 95 recognized αvβ3 and αvβ5 on human tumor cells but not mouse angiogenic integrins, CNTO 95 (10 mg/kg, 3 times/week) inhibited growth of human melanoma tumors in nude mice by approximately 80% (p = 0.0005), suggesting that CNTO 95 inhibited human tumor growth independently of its antiangiogenic activity. In a nude rat human xenograft model where CNTO 95 binds and blocks both tumor and host integrins, this antibody (10 mg/kg once/week) reduced final tumor weight by >99% (p < 0.0001). Based on these preclinical data, a dose-escalating phase I clinical trial in cancer patients has been initiated. To our knowledge, CNTO 95 is the first fully human MAb to αv integrins that has potent antitumor and antiangiogenic properties in in vivo preclinical models. © 2004 Wiley-Liss, Inc.
Bioorganic & Medicinal Chemistry Letters, 2001
Scientists are deeply concerned with the state of vulnerability of groundwater reservoirs. It is ... more Scientists are deeply concerned with the state of vulnerability of groundwater reservoirs. It is a complex task because of the difficulties in determining the degree of pollution of the ground water. Many methods have been adopted like DRASTIC, GOD, SI, SINTACS, etc. The present article targets the determination of the vulnerability of groundwater reservoirs of a climatic Mediterranean region (Nil valley region, Jijel). The excessive use of fertilizers in agriculture has been the main reason behind the increase of the Nil valley groundwater pollution with nitrates (Jijel, North-East Algeria). In fact, the use of fertilizers in high quantities relatively to the needs of the plants lead to the leaching and infiltration of the excess fertilizers into groundwater which increases the nitrates percentage; as a result, the allowed norms of water consumption are exceeded. Relevant to this, the aim of this study was to assess the aquifer vulnerability caused by pollution with nitrates using DRASTIC, GOD and SI methods. The spatial distribution of the found nitrates in groundwater shows that the DRASTIC method is the most appropriate method in this case with a percentage of 71% vs. 54 and 63% for GOD and SI methods, respectively. Moreover, it was found that the studied water is characterized by a medium to high degree of vulnerability. Pertinent to this, it is highly recommended to find solutions to better protect and preserve the Nil valley groundwater.
GPIIb/IIIa and ␣v3. We used chimeric (c) 7E3 Fab (ReoPro) and murine (m) 7E3 F(ab) 2 to elucidat... more GPIIb/IIIa and ␣v3. We used chimeric (c) 7E3 Fab (ReoPro) and murine (m) 7E3 F(ab) 2 to elucidate the role of these integrins in angiogenesis, tumor growth, and metastasis. These antibodies are potent inhibitors of GPIIb/IIIa and ␣v3. c7E3 Fab inhibited ␣v3-mediated human umbilical vein endothelial (HUVEC) and melanoma cell adhesion, migration, invasion, and basic fibroblast growth factor stimulated proliferation of HUVECs (IC 50 values range from 0.15 to 5 g/ml for different assays). In an in vitro angiogenesis assay, c7E3 Fab inhibited basic fibroblast growth factor and platelet-stimulated capillary formation of HUVECs (IC 50 ؍ 10 g/ml and 15 g/ml, respectively), demonstrating that endothelial ␣v3 is important for sprouting, and platelet-stimulated sprouting is mediated by GPIIb/IIIa. In an experimental metastasis assay, a single pretreatment of human melanoma cells with c7E3 Fab (2.5 g/ml) inhibited lung colonization of the tumor cells in severe combined immunodeficient mice. In vivo, m7E3 F(ab) 2 partially inhibited growth of human melanoma tumors in nude mice compared with control-treated animals. These data suggest that tumor cell-expressed integrins are important but not the only component involved in tumor growth. Because c7E3 Fab and m7E3 F(ab) 2 do not cross-react with murine integrins, this inhibition of metastasis and tumor growth is attributable to direct blockade of human tumor ␣v3 integrins. m7E3 F(ab) 2 completely blocked tumor formation and growth of human melanoma tumors growing in nude rats. In this xenograft model, m7E3 F(ab) 2 simultaneously binds to both human tumor and host platelet GPIIb/IIIa and endothelial ␣v3 integrins, thus participating as an antiangiogenic and an antitumor agent. Collectively, these results indicate that combined blockade of GPIIb/IIIa and ␣v3 affords significant antiangiogenic and antitumor benefit.
International Journal of Cancer, 2004
Integrins of the αv family, such as αvβ3 and αvβ5, are implicated in tumor-induced angiogenesis; ... more Integrins of the αv family, such as αvβ3 and αvβ5, are implicated in tumor-induced angiogenesis; but their role in tumor growth has not been fully explored. CNTO 95 is a fully human antibody that recognizes the αv family of integrins and is likely to be less immunogenic in humans compared to chimeric or humanized antibodies. CNTO 95 bound to purified αvβ3 and αvβ5 with a Kd of approximately 200 pM and to αv integrin–expressing human cells with a Kd of 1–24 nM. In vitro, CNTO 95 inhibited human melanoma cell adhesion, migration and invasion at doses ranging 7–20 nM. In a rat aortic ring sprouting assay, CNTO 95 (approx. 70 nM) completely inhibited sprouting. Using a human melanoma xenograft model in nude mice wherein CNTO 95 recognized αvβ3 and αvβ5 on human tumor cells but not mouse angiogenic integrins, CNTO 95 (10 mg/kg, 3 times/week) inhibited growth of human melanoma tumors in nude mice by approximately 80% (p = 0.0005), suggesting that CNTO 95 inhibited human tumor growth independently of its antiangiogenic activity. In a nude rat human xenograft model where CNTO 95 binds and blocks both tumor and host integrins, this antibody (10 mg/kg once/week) reduced final tumor weight by >99% (p < 0.0001). Based on these preclinical data, a dose-escalating phase I clinical trial in cancer patients has been initiated. To our knowledge, CNTO 95 is the first fully human MAb to αv integrins that has potent antitumor and antiangiogenic properties in in vivo preclinical models. © 2004 Wiley-Liss, Inc.
Bioorganic & Medicinal Chemistry Letters, 2001
Scientists are deeply concerned with the state of vulnerability of groundwater reservoirs. It is ... more Scientists are deeply concerned with the state of vulnerability of groundwater reservoirs. It is a complex task because of the difficulties in determining the degree of pollution of the ground water. Many methods have been adopted like DRASTIC, GOD, SI, SINTACS, etc. The present article targets the determination of the vulnerability of groundwater reservoirs of a climatic Mediterranean region (Nil valley region, Jijel). The excessive use of fertilizers in agriculture has been the main reason behind the increase of the Nil valley groundwater pollution with nitrates (Jijel, North-East Algeria). In fact, the use of fertilizers in high quantities relatively to the needs of the plants lead to the leaching and infiltration of the excess fertilizers into groundwater which increases the nitrates percentage; as a result, the allowed norms of water consumption are exceeded. Relevant to this, the aim of this study was to assess the aquifer vulnerability caused by pollution with nitrates using DRASTIC, GOD and SI methods. The spatial distribution of the found nitrates in groundwater shows that the DRASTIC method is the most appropriate method in this case with a percentage of 71% vs. 54 and 63% for GOD and SI methods, respectively. Moreover, it was found that the studied water is characterized by a medium to high degree of vulnerability. Pertinent to this, it is highly recommended to find solutions to better protect and preserve the Nil valley groundwater.