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Your search keyword '"Eccles, Suzanne A"' showing total 7 results
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7 results on '"Eccles, Suzanne A"'

1. Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma

Author

UU BETA RESEARCH, Poon, Evon, Liang, Tong, Jamin, Yann, Walz, Susanne, Kwok, Colin, Hakkert, Anne, Barker, Karen, Urban, Zuzanna, Thway, Khin, Zeid, Rhamy, Hallsworth, Albert, Box, Gary, Ebus, Marli E, Licciardello, Marco P, Sbirkov, Yordan, Lazaro, Glori, Calton, Elizabeth, Costa, Barbara M, Valenti, Melanie, De Haven Brandon, Alexis, Webber, Hannah, Tardif, Nicolas, Almeida, Gilberto S, Christova, Rossitza, Boysen, Gunther, Richards, Mark W, Barone, Giuseppe, Ford, Anthony, Bayliss, Richard, Clarke, Paul A, De Bono, Johann, Gray, Nathanael S, Blagg, Julian, Robinson, Simon P, Eccles, Suzanne A, Zheleva, Daniella, Bradner, James E, Molenaar, Jan, Vivanco, Igor, Eilers, Martin, Workman, Paul, Lin, Charles Y, Chesler, Louis, UU BETA RESEARCH, Poon, Evon, Liang, Tong, Jamin, Yann, Walz, Susanne, Kwok, Colin, Hakkert, Anne, Barker, Karen, Urban, Zuzanna, Thway, Khin, Zeid, Rhamy, Hallsworth, Albert, Box, Gary, Ebus, Marli E, Licciardello, Marco P, Sbirkov, Yordan, Lazaro, Glori, Calton, Elizabeth, Costa, Barbara M, Valenti, Melanie, De Haven Brandon, Alexis, Webber, Hannah, Tardif, Nicolas, Almeida, Gilberto S, Christova, Rossitza, Boysen, Gunther, Richards, Mark W, Barone, Giuseppe, Ford, Anthony, Bayliss, Richard, Clarke, Paul A, De Bono, Johann, Gray, Nathanael S, Blagg, Julian, Robinson, Simon P, Eccles, Suzanne A, Zheleva, Daniella, Bradner, James E, Molenaar, Jan, Vivanco, Igor, Eilers, Martin, Workman, Paul, Lin, Charles Y, and Chesler, Louis

Published
2020

2. Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma

Author

UU BETA RESEARCH, Poon, Evon, Liang, Tong, Jamin, Yann, Walz, Susanne, Kwok, Colin, Hakkert, Anne, Barker, Karen, Urban, Zuzanna, Thway, Khin, Zeid, Rhamy, Hallsworth, Albert, Box, Gary, Ebus, Marli E, Licciardello, Marco P, Sbirkov, Yordan, Lazaro, Glori, Calton, Elizabeth, Costa, Barbara M, Valenti, Melanie, De Haven Brandon, Alexis, Webber, Hannah, Tardif, Nicolas, Almeida, Gilberto S, Christova, Rossitza, Boysen, Gunther, Richards, Mark W, Barone, Giuseppe, Ford, Anthony, Bayliss, Richard, Clarke, Paul A, De Bono, Johann, Gray, Nathanael S, Blagg, Julian, Robinson, Simon P, Eccles, Suzanne A, Zheleva, Daniella, Bradner, James E, Molenaar, Jan, Vivanco, Igor, Eilers, Martin, Workman, Paul, Lin, Charles Y, Chesler, Louis, UU BETA RESEARCH, Poon, Evon, Liang, Tong, Jamin, Yann, Walz, Susanne, Kwok, Colin, Hakkert, Anne, Barker, Karen, Urban, Zuzanna, Thway, Khin, Zeid, Rhamy, Hallsworth, Albert, Box, Gary, Ebus, Marli E, Licciardello, Marco P, Sbirkov, Yordan, Lazaro, Glori, Calton, Elizabeth, Costa, Barbara M, Valenti, Melanie, De Haven Brandon, Alexis, Webber, Hannah, Tardif, Nicolas, Almeida, Gilberto S, Christova, Rossitza, Boysen, Gunther, Richards, Mark W, Barone, Giuseppe, Ford, Anthony, Bayliss, Richard, Clarke, Paul A, De Bono, Johann, Gray, Nathanael S, Blagg, Julian, Robinson, Simon P, Eccles, Suzanne A, Zheleva, Daniella, Bradner, James E, Molenaar, Jan, Vivanco, Igor, Eilers, Martin, Workman, Paul, Lin, Charles Y, and Chesler, Louis

Published
2020

3. Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma

Author

UU BETA RESEARCH, Poon, Evon, Liang, Tong, Jamin, Yann, Walz, Susanne, Kwok, Colin, Hakkert, Anne, Barker, Karen, Urban, Zuzanna, Thway, Khin, Zeid, Rhamy, Hallsworth, Albert, Box, Gary, Ebus, Marli E, Licciardello, Marco P, Sbirkov, Yordan, Lazaro, Glori, Calton, Elizabeth, Costa, Barbara M, Valenti, Melanie, De Haven Brandon, Alexis, Webber, Hannah, Tardif, Nicolas, Almeida, Gilberto S, Christova, Rossitza, Boysen, Gunther, Richards, Mark W, Barone, Giuseppe, Ford, Anthony, Bayliss, Richard, Clarke, Paul A, De Bono, Johann, Gray, Nathanael S, Blagg, Julian, Robinson, Simon P, Eccles, Suzanne A, Zheleva, Daniella, Bradner, James E, Molenaar, Jan, Vivanco, Igor, Eilers, Martin, Workman, Paul, Lin, Charles Y, Chesler, Louis, UU BETA RESEARCH, Poon, Evon, Liang, Tong, Jamin, Yann, Walz, Susanne, Kwok, Colin, Hakkert, Anne, Barker, Karen, Urban, Zuzanna, Thway, Khin, Zeid, Rhamy, Hallsworth, Albert, Box, Gary, Ebus, Marli E, Licciardello, Marco P, Sbirkov, Yordan, Lazaro, Glori, Calton, Elizabeth, Costa, Barbara M, Valenti, Melanie, De Haven Brandon, Alexis, Webber, Hannah, Tardif, Nicolas, Almeida, Gilberto S, Christova, Rossitza, Boysen, Gunther, Richards, Mark W, Barone, Giuseppe, Ford, Anthony, Bayliss, Richard, Clarke, Paul A, De Bono, Johann, Gray, Nathanael S, Blagg, Julian, Robinson, Simon P, Eccles, Suzanne A, Zheleva, Daniella, Bradner, James E, Molenaar, Jan, Vivanco, Igor, Eilers, Martin, Workman, Paul, Lin, Charles Y, and Chesler, Louis

Published
2020

4. MIR21 drives resistance to Heat Shock Protein 90 inhibition in cholangiocarcinoma

Author

Lampis, Andrea, Carotenuto, Pietro, Vlachogiannis, Georgios, Cascione, Luciano, Hedayat, Somaieh, Burke, Rosemary, Clarke, Paul, Bosma, Else, Simbolo, Michele, Scarpa, Aldo, Yu, Sijia, Cole, Rebecca, Smyth, Elizabeth, Mateos, Javier Fernández, Begum, Ruwaida, Hezelova, Blanka, Eltahir, Zakaria, Wotherspoon, Andrew, Fotiadis, Nicos, Bali, Maria Antonietta, Nepal, Chirag, Khan, Khurum, Stubbs, Mark, Hahne, Jens C, Gasparini, Pierluigi, Guzzardo, Vincenza, Croce, Carlo M, Eccles, Suzanne, Fassan, Matteo, Cunningham, David, Andersen, Jesper B, Workman, Paul, Valeri, Nicola, Braconi, Chiara, Lampis, Andrea, Carotenuto, Pietro, Vlachogiannis, Georgios, Cascione, Luciano, Hedayat, Somaieh, Burke, Rosemary, Clarke, Paul, Bosma, Else, Simbolo, Michele, Scarpa, Aldo, Yu, Sijia, Cole, Rebecca, Smyth, Elizabeth, Mateos, Javier Fernández, Begum, Ruwaida, Hezelova, Blanka, Eltahir, Zakaria, Wotherspoon, Andrew, Fotiadis, Nicos, Bali, Maria Antonietta, Nepal, Chirag, Khan, Khurum, Stubbs, Mark, Hahne, Jens C, Gasparini, Pierluigi, Guzzardo, Vincenza, Croce, Carlo M, Eccles, Suzanne, Fassan, Matteo, Cunningham, David, Andersen, Jesper B, Workman, Paul, Valeri, Nicola, and Braconi, Chiara

Abstract

BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small molecule compounds that are active against CCAs. Levels of microRNA 21 (MIR21 or miRNA21) are increased in CCAs. We investigated whether miRNA21 mediates resistance of CCA cells and organoids to HSP90 inhibitors.METHODS: We performed a high-throughput screen of 484 small molecule compounds to identify those that reduced viability of 6 human CCA cell lines. We tested the effects of HSP90 inhibitors on cells with disruption of the MIR21 gene, cells incubated with MIR21 inhibitors, and stable cell lines with inducible expression of MIR21. We obtained CCA biopsies from patients, cultured them as organoids (patient-derived organoids, PDOs). We assessed their architecture, mutation and gene expression patterns, response to compounds in culture, and when grown as subcutaneous xenograft tumors in mice.RESULTS: Cells with IDH1 and PBRM1 mutations had the highest level of sensitivity to histone deacetylase inhibitors. HSP90 inhibitors were effective in all cell lines, irrespective of mutations. Sensitivity of cells to HSP90 inhibitors correlated inversely with baseline level of MIR21. Disruption of MIR21 increased cell sensitivity to HSP90 inhibitors. CCA cells that expressed transgenic MIR21 were more resistant to HSP90 inhibitors than cells transfected with control vectors; inactivation of MIR21 in these cells restored sensitivity to these agents. MIR21 was shown to target the DnaJ heatshockprotein family (Hsp40) member B5 (DNAJB5). Transgenic expression of DNAJB5 in CCA cells that overexpressed MIR21 re-sensitized them to HSP90 inhibitors. Sensitivity of PDOs to HSP90 inhibitors, in culture and when grown as xenograft tumors in mice, depended on expression of miRNA21.CONCLUSIONS: miRNA21 appears to mediate resistance of CCA cells to HSP90 inhibitors by reducing levels of DNAJB5. HSP90 inhibitor

Published
2018

5. MIR21 drives resistance to Heat Shock Protein 90 inhibition in cholangiocarcinoma

Author

Lampis, Andrea, Carotenuto, Pietro, Vlachogiannis, Georgios, Cascione, Luciano, Hedayat, Somaieh, Burke, Rosemary, Clarke, Paul, Bosma, Else, Simbolo, Michele, Scarpa, Aldo, Yu, Sijia, Cole, Rebecca, Smyth, Elizabeth, Mateos, Javier Fernández, Begum, Ruwaida, Hezelova, Blanka, Eltahir, Zakaria, Wotherspoon, Andrew, Fotiadis, Nicos, Bali, Maria Antonietta, Nepal, Chirag, Khan, Khurum, Stubbs, Mark, Hahne, Jens C, Gasparini, Pierluigi, Guzzardo, Vincenza, Croce, Carlo M, Eccles, Suzanne, Fassan, Matteo, Cunningham, David, Andersen, Jesper B, Workman, Paul, Valeri, Nicola, Braconi, Chiara, Lampis, Andrea, Carotenuto, Pietro, Vlachogiannis, Georgios, Cascione, Luciano, Hedayat, Somaieh, Burke, Rosemary, Clarke, Paul, Bosma, Else, Simbolo, Michele, Scarpa, Aldo, Yu, Sijia, Cole, Rebecca, Smyth, Elizabeth, Mateos, Javier Fernández, Begum, Ruwaida, Hezelova, Blanka, Eltahir, Zakaria, Wotherspoon, Andrew, Fotiadis, Nicos, Bali, Maria Antonietta, Nepal, Chirag, Khan, Khurum, Stubbs, Mark, Hahne, Jens C, Gasparini, Pierluigi, Guzzardo, Vincenza, Croce, Carlo M, Eccles, Suzanne, Fassan, Matteo, Cunningham, David, Andersen, Jesper B, Workman, Paul, Valeri, Nicola, and Braconi, Chiara

Abstract

BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small molecule compounds that are active against CCAs. Levels of microRNA 21 (MIR21 or miRNA21) are increased in CCAs. We investigated whether miRNA21 mediates resistance of CCA cells and organoids to HSP90 inhibitors.METHODS: We performed a high-throughput screen of 484 small molecule compounds to identify those that reduced viability of 6 human CCA cell lines. We tested the effects of HSP90 inhibitors on cells with disruption of the MIR21 gene, cells incubated with MIR21 inhibitors, and stable cell lines with inducible expression of MIR21. We obtained CCA biopsies from patients, cultured them as organoids (patient-derived organoids, PDOs). We assessed their architecture, mutation and gene expression patterns, response to compounds in culture, and when grown as subcutaneous xenograft tumors in mice.RESULTS: Cells with IDH1 and PBRM1 mutations had the highest level of sensitivity to histone deacetylase inhibitors. HSP90 inhibitors were effective in all cell lines, irrespective of mutations. Sensitivity of cells to HSP90 inhibitors correlated inversely with baseline level of MIR21. Disruption of MIR21 increased cell sensitivity to HSP90 inhibitors. CCA cells that expressed transgenic MIR21 were more resistant to HSP90 inhibitors than cells transfected with control vectors; inactivation of MIR21 in these cells restored sensitivity to these agents. MIR21 was shown to target the DnaJ heatshockprotein family (Hsp40) member B5 (DNAJB5). Transgenic expression of DNAJB5 in CCA cells that overexpressed MIR21 re-sensitized them to HSP90 inhibitors. Sensitivity of PDOs to HSP90 inhibitors, in culture and when grown as xenograft tumors in mice, depended on expression of miRNA21.CONCLUSIONS: miRNA21 appears to mediate resistance of CCA cells to HSP90 inhibitors by reducing levels of DNAJB5. HSP90 inhibitor

Published
2018

6. The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma

Author

Berry, Teeara, Luther, William, Bhatnagar, Namrata, Jamin, Yann, Poon, Evon, Sanda, Takaomi, Pei, Desheng, Sharma, Bandana, Vetharoy, Winston R, Hallsworth, Albert, Ahmad, Zai, Barker, Karen, Moreau, Lisa, Webber, Hannah, Wang, Wenchao, Liu, Qingsong, Perez-Atayde, Antonio, Rodig, Scott, Cheung, Nai-Kong, Raynaud, Florence, Hallberg, Bengt, Robinson, Simon P, Gray, Nathanael S, Pearson, Andrew DJ, Eccles, Suzanne A, Chesler, Louis, George, Rani E, Berry, Teeara, Luther, William, Bhatnagar, Namrata, Jamin, Yann, Poon, Evon, Sanda, Takaomi, Pei, Desheng, Sharma, Bandana, Vetharoy, Winston R, Hallsworth, Albert, Ahmad, Zai, Barker, Karen, Moreau, Lisa, Webber, Hannah, Wang, Wenchao, Liu, Qingsong, Perez-Atayde, Antonio, Rodig, Scott, Cheung, Nai-Kong, Raynaud, Florence, Hallberg, Bengt, Robinson, Simon P, Gray, Nathanael S, Pearson, Andrew DJ, Eccles, Suzanne A, Chesler, Louis, and George, Rani E

Abstract

The ALK(F1174L) mutation is associated with intrinsic and acquired resistance to crizotinib and cosegregates with MYCN in neuroblastoma. In this study, we generated a mouse model overexpressing ALK(F1174L) in the neural crest. Compared to ALKF1174L and MYCN alone, co-expression of these two oncogenes led to the development of neuroblastomas with earlier onset, higher penetrance, and enhanced lethality. ALK(F1174L)/MYCN tumors exhibited increased MYCN dosage due to ALK(F1174L)-induced activation of the PI3K/AKT/mTOR and MAPK pathways, coupled with suppression of MYCN pro-apoptotic effects. Combined treatment with the ATP-competitive mTOR inhibitor Torin2 overcame the resistance of ALK(F1174L)/MYCN tumors to crizotinib. Our findings demonstrate a pathogenic role for ALK(F1174L) in neuroblastomas overexpressing MYCN and suggest a strategy for improving targeted therapy for ALK-positive neuroblastoma.

Published
2012
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7. Preclinical drug development must consider the impact on metastasis

Author

Steeg, Patricia, Anderson, Robin, Bar-Eli, Menashe, Chambers, Ann, Eccles, Suzanne, Hunter, Kent, Itoh, Kazuyuki, Kang, Yibin, Matrisian, Lynn, Sleeman, Jonathan, Theodorescu, Dan, Thompson, Rik, Welch, Danny, Steeg, Patricia, Anderson, Robin, Bar-Eli, Menashe, Chambers, Ann, Eccles, Suzanne, Hunter, Kent, Itoh, Kazuyuki, Kang, Yibin, Matrisian, Lynn, Sleeman, Jonathan, Theodorescu, Dan, Thompson, Rik, and Welch, Danny

Abstract

Recently, two landmark reports on antiangiogenic therapy were published: Paez-Ribes and colleagues and Ebos and colleagues . The Board of the Metastasis Research Society (MRS) congratulates the authors for their informative articles that help to explain the puzzle of why antiangiogenic agents have had a relatively minor or no significant impact on patient survival. Using four model systems and several different strategies, these researchers showed that inhibition of angiogenesis reduced primary tumor growth and microvessel density in keeping with many earlier reports, but strikingly, accelerated invasion and metastasis.

Published
2009

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