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1. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial

Author

Parnis, Francis, Joshua, Anthony M., Horvath, Lisa G., Steer, Christopher, Marx, Gavin, Sandhu, Shahneen, Gurney, Howard, Ferguson, Thomas, Van Bruwaene, Siska, Luyten, Daisy, Schatteman, Peter, Lumen, Nicolaas, Dirix, Luc, Goeminne, Jean-Charles, Gil, Thierry, Seront, Emmanuel, Vulsteke, Christof, Kussumoto, Celio, Franke, Fabio A., Martinelli de Oliveira, Fabricio Augusto, Pereira de Santana Gomes, Andrea Juliana, Pinczowski, Hélio, Preto, Daniel D'Almeida, Zucca, Luis Eduardo, Borges, Giuliano Santos, Murad, Andre M., Saad, Fred, Chi, Kim N., Fradet, Yves, Fleshner, Neil E., Emmenegger, Urban, Brasso, Klaus, Fizazi, Karim, Culine, Stephane, Thiery-Vuillemin, Antoine, Joly, Florence, Fléchon, Aude, Hilgers, Werner, Eymard, Jean-Christophe, Borchiellini, Delphine, Barthélémy, Philippe, Berger, Raanan, Leibowitz-Amit, Raya, Mermershtain, Wilmosh, Rouvinov, Keren, Peer, Avivit, Kovel, Svetlana, Sella, Avishay, Lolkema, Martijn P., van den Eertwegh, Alfonsus J.M., Voortman, Johannes, Aarts, Maureen J., Gietema, Jourik A., Kim, Choung-Soo, Choi, Young-Deuk, Chung, Byung-Ha, Gafanov, Rustem A., Kopyltsov, Evgeniy, Usynin, Evgeny A., Carles, Joan, Mellado, Begoña, Maroto, José Pablo, García-Donás, Jesús, Rodríguez Moreno, Juan Francisco, Durán, Ignacio, Pérez-Valderrama, Begoña, Castro, Elena, Olmos, David, Méndez-Vidal, María José, Estellés, David Lorente, Sarrió, Regina Gironés, Muñoz-Langa, José, Herranz, Urbano Anido, Puente Vázquez, Javier, Castellanos, Enrique, Hellström, Martin, Widmark, Anders, Lissbrant, Ingela Franck, Jellvert, Åsa, Külich, Cecilia, Blom, René, Ståhl, Olof, Chiang, Po-Hui, Kang, Chih-Hsiung, Ou, Yen-Chuan, Wang, Shian-Shiang, Wu, Hsi-Chin, Lu, Yu-Chuan, Attard, Gerhardt, Khoo, Vincent, Bahl, Amit, Kellati, Prasad, Parikh, Omi, Srinivasan, Rajaguru, Lester, Jason F., Staffurth, John N., Cheng, Heather H., Efstathiou, Eleni, Pilié, Patrick G., George, Daniel J., Karsh, Lawrence I., Kelly, W. Kevin, Danila, Daniel C., Sieber, Paul R., Smith, Matthew R., Heath, Elisabeth I., Vaishampayan, Ulka N., Flaig, Thomas W., Emamekhoo, Hamid, Pinski, Jacek K., Kalebasty, Arash Rezazadeh, Maly, Joseph J., Moon, Helen, Smith, Matthew R, Scher, Howard I, Lara, Primo N, Jr, Yu, Evan Y, George, Daniel J, Chi, Kim N, Danila, Daniel C, Mason, Gary E, Espina, Byron M, Zhao, Xin, Urtishak, Karen A, Francis, Peter, and Lopez-Gitlitz, Angela

Published
2022
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3. Supplementary figure legend from ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody–Drug Conjugate Treatment

Author

Lamberts, Laetitia E., primary, Menke-van der Houven van Oordt, Catharina W., primary, ter Weele, Eva J., primary, Bensch, Frederike, primary, Smeenk, Michiel M., primary, Voortman, Johannes, primary, Hoekstra, Otto S., primary, Williams, Simon P., primary, Fine, Bernard M., primary, Maslyar, Daniel, primary, de Jong, Johan R., primary, Gietema, Jourik A., primary, Schröder, Carolien P., primary, Bongaerts, Alphons H.H., primary, Lub-de Hooge, Marjolijn N., primary, Verheul, Henk M.W., primary, Sanabria Bohorquez, Sandra M., primary, Glaudemans, Andor W.J.M., primary, and de Vries, Elisabeth G.E., primary

Published
2023
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4. Supplementary figure 1A from ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody–Drug Conjugate Treatment

Author

Lamberts, Laetitia E., primary, Menke-van der Houven van Oordt, Catharina W., primary, ter Weele, Eva J., primary, Bensch, Frederike, primary, Smeenk, Michiel M., primary, Voortman, Johannes, primary, Hoekstra, Otto S., primary, Williams, Simon P., primary, Fine, Bernard M., primary, Maslyar, Daniel, primary, de Jong, Johan R., primary, Gietema, Jourik A., primary, Schröder, Carolien P., primary, Bongaerts, Alphons H.H., primary, Lub-de Hooge, Marjolijn N., primary, Verheul, Henk M.W., primary, Sanabria Bohorquez, Sandra M., primary, Glaudemans, Andor W.J.M., primary, and de Vries, Elisabeth G.E., primary

Published
2023
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5. Supplementary Figures 1-3, Tables 1-6 from Loss of 18q22.3 Involving the Carboxypeptidase of Glutamate-like Gene Is Associated with Poor Prognosis in Resected Pancreatic Cancer

Author

Lee, Jih-Hsiang, primary, Giovannetti, Elisa, primary, Hwang, Jin-Hyeok, primary, Petrini, Iacopo, primary, Wang, Qiuyan, primary, Voortman, Johannes, primary, Wang, Yonghong, primary, Steinberg, Seth M., primary, Funel, Niccola, primary, Meltzer, Paul S., primary, Wang, Yisong, primary, and Giaccone, Giuseppe, primary

Published
2023
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6. Data from MicroRNA Expression and Clinical Outcomes in Patients Treated with Adjuvant Chemotherapy after Complete Resection of Non–Small Cell Lung Carcinoma

Author

Voortman, Johannes, primary, Goto, Akiteru, primary, Mendiboure, Jean, primary, Sohn, Jane J., primary, Schetter, Aaron J., primary, Saito, Motonobu, primary, Dunant, Ariane, primary, Pham, Trung C., primary, Petrini, Iacopo, primary, Lee, Alan, primary, Khan, Mohammed A., primary, Hainaut, Pierre, primary, Pignon, Jean-Pierre, primary, Brambilla, Elisabeth, primary, Popper, Helmut H., primary, Filipits, Martin, primary, Harris, Curtis C., primary, and Giaccone, Giuseppe, primary

Published
2023
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7. Supplementary Figure 1 from MicroRNA Expression and Clinical Outcomes in Patients Treated with Adjuvant Chemotherapy after Complete Resection of Non–Small Cell Lung Carcinoma

Author

Voortman, Johannes, primary, Goto, Akiteru, primary, Mendiboure, Jean, primary, Sohn, Jane J., primary, Schetter, Aaron J., primary, Saito, Motonobu, primary, Dunant, Ariane, primary, Pham, Trung C., primary, Petrini, Iacopo, primary, Lee, Alan, primary, Khan, Mohammed A., primary, Hainaut, Pierre, primary, Pignon, Jean-Pierre, primary, Brambilla, Elisabeth, primary, Popper, Helmut H., primary, Filipits, Martin, primary, Harris, Curtis C., primary, and Giaccone, Giuseppe, primary

Published
2023
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8. Supplementary Tables 1-9 from MicroRNA Expression and Clinical Outcomes in Patients Treated with Adjuvant Chemotherapy after Complete Resection of Non–Small Cell Lung Carcinoma

Author

Voortman, Johannes, primary, Goto, Akiteru, primary, Mendiboure, Jean, primary, Sohn, Jane J., primary, Schetter, Aaron J., primary, Saito, Motonobu, primary, Dunant, Ariane, primary, Pham, Trung C., primary, Petrini, Iacopo, primary, Lee, Alan, primary, Khan, Mohammed A., primary, Hainaut, Pierre, primary, Pignon, Jean-Pierre, primary, Brambilla, Elisabeth, primary, Popper, Helmut H., primary, Filipits, Martin, primary, Harris, Curtis C., primary, and Giaccone, Giuseppe, primary

Published
2023
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9. Supplementary Appendix 1 from MicroRNA Expression and Clinical Outcomes in Patients Treated with Adjuvant Chemotherapy after Complete Resection of Non–Small Cell Lung Carcinoma

Author

Voortman, Johannes, primary, Goto, Akiteru, primary, Mendiboure, Jean, primary, Sohn, Jane J., primary, Schetter, Aaron J., primary, Saito, Motonobu, primary, Dunant, Ariane, primary, Pham, Trung C., primary, Petrini, Iacopo, primary, Lee, Alan, primary, Khan, Mohammed A., primary, Hainaut, Pierre, primary, Pignon, Jean-Pierre, primary, Brambilla, Elisabeth, primary, Popper, Helmut H., primary, Filipits, Martin, primary, Harris, Curtis C., primary, and Giaccone, Giuseppe, primary

Published
2023
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10. Niraparib in patients with metastatic castration-resistant prostate cancer and DNA repair gene defects (GALAHAD): a multicentre, open-label, phase 2 trial

Author

Smith, Matthew R, primary, Scher, Howard I, additional, Sandhu, Shahneen, additional, Efstathiou, Eleni, additional, Lara, Primo N, additional, Yu, Evan Y, additional, George, Daniel J, additional, Chi, Kim N, additional, Saad, Fred, additional, Ståhl, Olof, additional, Olmos, David, additional, Danila, Daniel C, additional, Mason, Gary E, additional, Espina, Byron M, additional, Zhao, Xin, additional, Urtishak, Karen A, additional, Francis, Peter, additional, Lopez-Gitlitz, Angela, additional, Fizazi, Karim, additional, Parnis, Francis, additional, Joshua, Anthony M., additional, Horvath, Lisa G., additional, Steer, Christopher, additional, Marx, Gavin, additional, Gurney, Howard, additional, Ferguson, Thomas, additional, Van Bruwaene, Siska, additional, Luyten, Daisy, additional, Schatteman, Peter, additional, Lumen, Nicolaas, additional, Dirix, Luc, additional, Goeminne, Jean-Charles, additional, Gil, Thierry, additional, Seront, Emmanuel, additional, Vulsteke, Christof, additional, Kussumoto, Celio, additional, Franke, Fabio A., additional, Martinelli de Oliveira, Fabricio Augusto, additional, Pereira de Santana Gomes, Andrea Juliana, additional, Pinczowski, Hélio, additional, Preto, Daniel D'Almeida, additional, Zucca, Luis Eduardo, additional, Borges, Giuliano Santos, additional, Murad, Andre M., additional, Chi, Kim N., additional, Fradet, Yves, additional, Fleshner, Neil E., additional, Emmenegger, Urban, additional, Brasso, Klaus, additional, Culine, Stephane, additional, Thiery-Vuillemin, Antoine, additional, Joly, Florence, additional, Fléchon, Aude, additional, Hilgers, Werner, additional, Eymard, Jean-Christophe, additional, Borchiellini, Delphine, additional, Barthélémy, Philippe, additional, Berger, Raanan, additional, Leibowitz-Amit, Raya, additional, Mermershtain, Wilmosh, additional, Rouvinov, Keren, additional, Peer, Avivit, additional, Kovel, Svetlana, additional, Sella, Avishay, additional, Lolkema, Martijn P., additional, van den Eertwegh, Alfonsus J.M., additional, Voortman, Johannes, additional, Aarts, Maureen J., additional, Gietema, Jourik A., additional, Kim, Choung-Soo, additional, Choi, Young-Deuk, additional, Chung, Byung-Ha, additional, Gafanov, Rustem A., additional, Kopyltsov, Evgeniy, additional, Usynin, Evgeny A., additional, Carles, Joan, additional, Mellado, Begoña, additional, Maroto, José Pablo, additional, García-Donás, Jesús, additional, Rodríguez Moreno, Juan Francisco, additional, Durán, Ignacio, additional, Pérez-Valderrama, Begoña, additional, Castro, Elena, additional, Méndez-Vidal, María José, additional, Estellés, David Lorente, additional, Sarrió, Regina Gironés, additional, Muñoz-Langa, José, additional, Herranz, Urbano Anido, additional, Puente Vázquez, Javier, additional, Castellanos, Enrique, additional, Hellström, Martin, additional, Widmark, Anders, additional, Lissbrant, Ingela Franck, additional, Jellvert, Åsa, additional, Külich, Cecilia, additional, Blom, René, additional, Chiang, Po-Hui, additional, Kang, Chih-Hsiung, additional, Ou, Yen-Chuan, additional, Wang, Shian-Shiang, additional, Wu, Hsi-Chin, additional, Lu, Yu-Chuan, additional, Attard, Gerhardt, additional, Khoo, Vincent, additional, Bahl, Amit, additional, Kellati, Prasad, additional, Parikh, Omi, additional, Srinivasan, Rajaguru, additional, Lester, Jason F., additional, Staffurth, John N., additional, Cheng, Heather H., additional, Pilié, Patrick G., additional, George, Daniel J., additional, Karsh, Lawrence I., additional, Kelly, W. Kevin, additional, Danila, Daniel C., additional, Sieber, Paul R., additional, Smith, Matthew R., additional, Heath, Elisabeth I., additional, Vaishampayan, Ulka N., additional, Flaig, Thomas W., additional, Emamekhoo, Hamid, additional, Pinski, Jacek K., additional, Kalebasty, Arash Rezazadeh, additional, Maly, Joseph J., additional, and Moon, Helen, additional

Published
2022
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12. Prediction of outcome of non-small cell lung cancer patients treated with chemotherapy and bortezomib by time-course MALDI-TOF-MS serum peptide profiling

Author

Giaccone Giuseppe, Knol Jaco C, Pham Thang V, Voortman Johannes, and Jimenez Connie R

Subjects
Cytology, QH573-671
Abstract

Abstract Background Only a minority of patients with advanced non-small cell lung cancer (NSCLC) benefit from chemotherapy. Serum peptide profiling of NSCLC patients was performed to investigate patterns associated with treatment outcome. Using magnetic bead-assisted serum peptide capture coupled to matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS), serum peptide mass profiles of 27 NSCLC patients treated with cisplatin-gemcitabine chemotherapy and bortezomib were obtained. Support vector machine-based algorithms to predict clinical outcome were established based on differential pre-treatment peptide profiles and dynamic changes in peptide abundance during treatment. Results A 6-peptide ion signature distinguished with 82% accuracy, sensitivity and specificity patients with a relatively short vs. long progression-free survival (PFS) upon treatment. Prediction of long PFS was associated with longer overall survival. Inclusion of 7 peptide ions showing differential changes in abundance during treatment led to a 13-peptide ion signature with 86% accuracy at 100% sensitivity and 73% specificity. A 5-peptide ion signature could separate patients with a partial response vs. non-responders with 89% accuracy at 100% sensitivity and 83% specificity. Differential peptide profiles were also found when comparing the NSCLC serum profiles to those from cancer-free control subjects. Conclusion This study shows that serum peptidome profiling using MALDI-TOF-MS coupled to pattern diagnostics may aid in prediction of treatment outcome of advanced NSCLC patients treated with chemotherapy.

Published
2009
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13. Phase I Study of Dalteparin in Combination With Sunitinib in Patients With Metastatic Clear Cell Renal Carcinoma

Author

Wentink, Madelon Q., Verheul, Henk M.W., Pal, Sumanta K., George, Saby, Voortman, Johannes, Danchaivijitr, Pongwut, Adelaiye, Remi, Poslinski, Diane, Groman, Adrienne, Hutson, Alan, and Pili, Roberto

Abstract

The processes of angiogenesis and coagulation are highly interconnected. This phase I trial investigated the TKI sunitinib in combination with the LMWH dalteparin in patients with metastatic renal cell carcinoma. In 3 dose cohorts and a separate expansion cohort, 17 patients were included. Combination treatment was safe and without increased incidence of bleeding events.

Published
2024
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15. High-dose, intermittent sunitinib as an alternative treatment strategy

Author

Rovithi, Maria, de Haas, Richard R., Honeywell, Richard J., Voortman, Johannes, Griffioen, Arjan W., Labots, Mariette, Luik, Anne Marije, Peters, Godefridus J., Broxterman, Henk J., Verheul, Henk M. W., Medical oncology, CCA - Innovative therapy, and Medical oncology laboratory

Published
2014

16. Molecular Mechanisms Underlying the Role of MicroRNAs in the Chemoresistance of Pancreatic Cancer

Author

Garajová, Ingrid, Le Large, Tessa Y., Frampton, Adam E., Rolfo, Christian, Voortman, Johannes, and Giovannetti, Elisa

Subjects
Article Subject
Abstract

Pancreatic ductal adenocarcinoma (PDAC) is an extremely severe disease where the mortality and incidence rates are almost identical. This is mainly due to late diagnosis and limited response to current treatments. The tumor macroenvironment/microenvironment have been frequently reported as the major contributors to chemoresistance in PDAC, preventing the drugs from reaching their intended site of action (i.e., the malignant duct cells). However, the recent discovery of microRNAs (miRNAs) has provided new directions for research on mechanisms underlying response to chemotherapy. Due to their tissue-/disease-specific expression and high stability in tissues and biofluids, miRNAs represent new promising diagnostic and prognostic/predictive biomarkers and therapeutic targets. Furthermore, several studies have documented that selected miRNAs, such as miR-21 and miR-34a, may influence response to chemotherapy in several tumor types, including PDAC. In this review, we summarize the current knowledge on the role of miRNAs in PDAC and recent advances in understanding their role in chemoresistance through multiple molecular mechanisms.

Published
2014
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18. ImmunoPET with Anti-Mesothelin Antibody in Patients with Pancreatic and Ovarian Cancer before Anti-Mesothelin Antibody–Drug Conjugate Treatment

Author

Lamberts, Laetitia E., primary, Menke-van der Houven van Oordt, Catharina W., additional, ter Weele, Eva J., additional, Bensch, Frederike, additional, Smeenk, Michiel M., additional, Voortman, Johannes, additional, Hoekstra, Otto S., additional, Williams, Simon P., additional, Fine, Bernard M., additional, Maslyar, Daniel, additional, de Jong, Johan R., additional, Gietema, Jourik A., additional, Schröder, Carolien P., additional, Bongaerts, Alphons H.H., additional, Lub-de Hooge, Marjolijn N., additional, Verheul, Henk M.W., additional, Sanabria Bohorquez, Sandra M., additional, Glaudemans, Andor W.J.M., additional, and de Vries, Elisabeth G.E., additional

Published
2016
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19. Phase I Study of DMOT4039A, an Antibody–Drug Conjugate Targeting Mesothelin, in Patients with Unresectable Pancreatic or Platinum-Resistant Ovarian Cancer

Author

Weekes, Colin D., primary, Lamberts, Laetitia E., additional, Borad, Mitesh J., additional, Voortman, Johannes, additional, McWilliams, Robert R., additional, Diamond, Jennifer R., additional, de Vries, Elisabeth G.E., additional, Verheul, Henk M., additional, Lieu, Christopher H., additional, Kim, George P., additional, Wang, Yulei, additional, Scales, Suzie J., additional, Samineni, Divya, additional, Brunstein, Flavia, additional, Choi, YounJeong, additional, Maslyar, Daniel J., additional, and Colon-Otero, Gerardo, additional

Published
2016
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21. A phase 1 study of weekly high dose sunitinib in patients with advanced solid tumors: Early signs of activity in non-RCC tumor types.

Author

Rovithi, Maria, primary, Voortman, Johannes, additional, Luik, Anne Marije, additional, Ruijter, Rita, additional, de Haas, Richard, additional, Honeywell, Richard, additional, Labots, Mariette, additional, Poel, Dennis, additional, Peters, Godefridus J., additional, Griffioen, Arjan W., additional, and Verheul, Henk M.W., additional

Published
2015
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23. MicroRNA expression and outcome of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer: International Adjuvant Lung Cancer Trial Biologic Program (IALT-Bio)

Author

Voortman, Johannes, Goto, Akiteru, Mendiboure, Jean, Sohn, Jane J., Schetter, Aaron J., Dunant, Ariane, Khan, Mohamed, Pham, Trung C., Petrini, Iacopo, Lee, Alan, Hainaut, Pierre, Pignon, Jean-Pierre, Brambilla, Elisabeth, Popper, Helmut H., Filipits, Martin, Harris, Curtis C., Giaccone, Giuseppe, and Internal medicine

Published
2010

25. A phase I study of DMOT4039A, an antibody-drug conjugate (ADC) targeting mesothelin (MSLN), in patients (pts) with unresectable pancreatic (PC) or platinum-resistant ovarian cancer (OC).

Author

Weekes, Colin D., primary, Lamberts, Laetitia E., additional, Borad, Mitesh J., additional, Voortman, Johannes, additional, McWilliams, Robert R., additional, Diamond, Jennifer Robinson, additional, De Vries, Elisabeth, additional, Verheul, Henk M.W., additional, Lieu, Christopher Hanyoung, additional, Yue, Huibin, additional, Wang, Yulei, additional, Scales, Suzie, additional, Samineni, Divya, additional, Wood, Katie, additional, Brunstein, Flavia, additional, Maslyar, Daniel J., additional, and Kim, George P., additional

Published
2014
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26. Loss of 18q22.3 Involving the Carboxypeptidase of Glutamate-like Gene Is Associated with Poor Prognosis in Resected Pancreatic Cancer

Author

Lee, Jih-Hsiang, primary, Giovannetti, Elisa, additional, Hwang, Jin-Hyeok, additional, Petrini, Iacopo, additional, Wang, Qiuyan, additional, Voortman, Johannes, additional, Wang, Yonghong, additional, Steinberg, Seth M., additional, Funel, Niccola, additional, Meltzer, Paul S., additional, Wang, Yisong, additional, and Giaccone, Giuseppe, additional

Published
2011
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29. MicroRNA Expression and Clinical Outcomes in Patients Treated with Adjuvant Chemotherapy after Complete Resection of Non–Small Cell Lung Carcinoma

Author

Voortman, Johannes, primary, Goto, Akiteru, additional, Mendiboure, Jean, additional, Sohn, Jane J., additional, Schetter, Aaron J., additional, Saito, Motonobu, additional, Dunant, Ariane, additional, Pham, Trung C., additional, Petrini, Iacopo, additional, Lee, Alan, additional, Khan, Mohammed A., additional, Hainaut, Pierre, additional, Pignon, Jean-Pierre, additional, Brambilla, Elisabeth, additional, Popper, Helmut H., additional, Filipits, Martin, additional, Harris, Curtis C., additional, and Giaccone, Giuseppe, additional

Published
2010
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30. Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer

Author

Hwang, Jin-Hyeok, primary, Voortman, Johannes, additional, Giovannetti, Elisa, additional, Steinberg, Seth M., additional, Leon, Leticia G., additional, Kim, Yong-Tae, additional, Funel, Niccola, additional, Park, Joo Kyung, additional, Kim, Min A., additional, Kang, Gyeong Hoon, additional, Kim, Sun-Whe, additional, Chiaro, Marco Del, additional, Peters, Godefridus J., additional, and Giaccone, Giuseppe, additional

Published
2010
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31. Abstract 3000: MicroRNA-21 as a biomarker for benefit from adjuvant therapy in resectable pancreatic adenocarcinoma

Author

Voortman, Johannes, primary, Hwang, Jin-Hyeok, additional, Giovannetti, Elisa, additional, Steinberg, Seth M., additional, Kim, Yong-Tae, additional, Funel, Niccola, additional, Park, Joo Kyung, additional, Kim, Min A., additional, Kang, Gyeong Hoon, additional, Kim, Sun-Whe, additional, Chiaro, Marco Del, additional, Peters, Godefridus J., additional, and Giaccone, Giuseppe, additional

Published
2010
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32. Abstract 2995: MicroRNA expression and outcome of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer: International Adjuvant Lung Cancer Trial Biologic Program (IALT-Bio)

Author

Voortman, Johannes, primary, Goto, Akiteru, additional, Mendiboure, Jean, additional, Sohn, Jane J., additional, Schetter, Aaron J., additional, Dunant, Ariane, additional, Khan, Mohamed, additional, Pham, Trung C., additional, Petrini, Iacopo, additional, Lee, Alan, additional, Hainaut, Pierre, additional, Pignon, Jean-Pierre, additional, Brambilla, Elisabeth, additional, Popper, Helmut H., additional, Filipits, Martin, additional, Harris, Curtis C., additional, and Giaccone, Giuseppe, additional

Published
2010
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35. Identification of MicroRNA-21 as a Biomarker for Chemoresistance and Clinical Outcome Following Adjuvant Therapy in Resectable Pancreatic Cancer.

Author

Jin-Hyeok Hwang, Voortman, Johannes, Giovannetti, Elisa, Steinberg, Seth M., Leon, Leticia G., Yong-Tae Kim, Funel, Niccola, Joo Kyung Park, Kim, Min A., Gyeong Hoon Kang, Sun-Whe Kim, del Chiaro, Marco, Peters, Godefridus J., and Giaccone, Giuseppe

Subjects
*BIOMARKERS, *PANCREATIC cancer, *ADJUVANT treatment of cancer, *SURGICAL excision, *HEALTH outcome assessment, *IMMUNOHISTOCHEMISTRY, *GENE expression, *ANTINEOPLASTIC agents, *KOREANS, *ITALIANS, *DISEASES
Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. The high risk of recurrence following surgical resection provides the rationale for adjuvant therapy. However, only a subset of patients benefit from adjuvant therapy. Identification of molecular markers to predict treatment outcome is therefore warranted. The aim of the present study was to evaluate whether expression of novel candidate biomarkers, including microRNAs, can predict clinical outcome in PDAC patients treated with adjuvant therapy. Methodology/Principal Findings: Formalin-fixed paraffin embedded specimens from a cohort of 82 resected Korean PDAC cases were analyzed for protein expression by immunohistochemistry and for microRNA expression using quantitative Real- Time PCR. Cox proportional hazards model analysis in the subgroup of patients treated with adjuvant therapy (N = 52) showed that lower than median miR-21 expression was associated with a significantly lower hazard ratio (HR) for death (HR = 0.316; 95%CI = 0.166-0.600; P = 0.0004) and recurrence (HR = 0.521; 95%CI = 0.280-0.967; P = 0.04). MiR-21 expression status emerged as the single most predictive biomarker for treatment outcome among all 27 biological and 9 clinicopathological factors evaluated. No significant association was detected in patients not treated with adjuvant therapy. In an independent validation cohort of 45 frozen PDAC tissues from Italian cases, all treated with adjuvant therapy, lower than median miR-21 expression was confirmed to be correlated with longer overall as well as disease-free survival. Furthermore, transfection with anti-miR-21 enhanced the chemosensitivity of PDAC cells. Conclusions Significance: Low miR-21 expression was associated with benefit from adjuvant treatment in two independent cohorts of PDAC cases, and anti-miR-21 increased anticancer drug activity in vitro. These data provide evidence that miR-21 may allow stratification for adjuvant therapy, and represents a new potential target for therapy in PDAC. [ABSTRACT FROM AUTHOR]

Published
2010
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37. Phase I Study of Dalteparin in Combination With Sunitinib in Patients With Metastatic Clear Cell Renal Carcinoma.

Author

Wentink MQ, Verheul HMW, Pal SK, George S, Voortman J, Danchaivijitr P, Adelaiye R, Poslinski D, Groman A, Hutson A, and Pili R

Abstract

Background: Based on the tumor-driven concomitant activation of angiogenesis and coagulation we conducted a phase I combination study of sunitinib with the low molecular weight heparin dalteparin in patients with metastatic clear cell renal cell carcinoma (ccRCC)., Materials and Methods: Patients received standard treatment with sunitinib (50 mg daily, 4 weeks on, 2 weeks off). During the second week of no sunitinib in the first cycle (week 6) patients received dalteparin monotherapy (in escalating doses). Combination therapy of the 2 agents was administered from the second cycle onward. Seventeen patients were enrolled at 3 dose levels of dalteparin., Results: Diarrhea and fatigue were the most frequent reported drug-related toxicities (41%). One dose-limiting toxicity (grade 3 anemia) was observed at the highest dose level of dalteparin. There were 4 partial responses (24%) and the median progression-free survival in this study was 14 months (95% confidence interval, 8.0-23.4). Anti-factor Xa levels were increased during combination therapy compared with dalteparin monotherapy., Conclusions: Combination therapy of sunitinib with therapeutic doses of dalteparin is safe and well tolerated. The increased anti-factor Xa levels during combination treatment suggest that sunitinib might increase the anticoagulation activity of dalteparin. The positive safety profile warrants prospective evaluation of the clinical benefit of this combination strategy in patients with ccRCC., (Copyright © 2017. Published by Elsevier Inc.)

Published
2017
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38. Response and toxicity prediction by MALDI-TOF-MS serum peptide profiling in patients with non-small cell lung cancer.

Author

Rovithi M, Lind JS, Pham TV, Voortman J, Knol JC, Verheul HM, Smit EF, and Jimenez CR

Subjects
Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Non-Small-Cell Lung blood, Carcinoma, Non-Small-Cell Lung genetics, Disease-Free Survival, ErbB Receptors genetics, Erlotinib Hydrochloride adverse effects, Erlotinib Hydrochloride therapeutic use, Humans, Lung Neoplasms blood, Lung Neoplasms genetics, Mutation, Niacinamide adverse effects, Niacinamide analogs & derivatives, Niacinamide therapeutic use, Phenylurea Compounds adverse effects, Phenylurea Compounds therapeutic use, Proto-Oncogene Proteins p21(ras) genetics, Sorafenib, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols adverse effects, Biomarkers, Tumor blood, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Peptides blood, Proteomics, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Abstract

Purpose: We validated a previously reported proteomic signature, associated with treatment outcome, in an independent cohort of patients with non-small cell lung cancer (NSCLC). A novel peptide signature was developed to predict toxicity., Experimental Design: Using automated magnetic C18 bead-assisted serum peptide capture coupled to MALDI-TOF MS, we conducted serum peptide profiling of 50 NCSLC patients participating in a phase II trial of erlotinib and sorafenib. On the obtained peptide mass profiles, we applied a previously described proteomic classification algorithm. Additionally, associations between observed side effects and peptide profiles were investigated., Results: Application of the previously acquired algorithm successfully classified the new cohort of patients in groups significantly associated with the outcome. The "poor" group exhibited shorter median progression-free survival (PFS) and overall survival (OS) of 1.35 and 1.98 months (with p = 0.00677 and p = 0.00002, respectively) while the "good" group had significantly longer PFS and OS (10.63 and 14.4 months with p = 0.00142 and p = 0.00002, respectively), compared to average OS and PFS. Two specific peptides were detected in the sera of all patients that developed severe toxicity., Conclusions and Clinical Relevance: Our results provide an algorithm that, following prospective validation in larger cohorts, could assist treatment selection of patients with NSCLC in the first line setting., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2016
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39. Loss of 18q22.3 involving the carboxypeptidase of glutamate-like gene is associated with poor prognosis in resected pancreatic cancer.

Author

Lee JH, Giovannetti E, Hwang JH, Petrini I, Wang Q, Voortman J, Wang Y, Steinberg SM, Funel N, Meltzer PS, Wang Y, and Giaccone G

Subjects
Aged, Aged, 80 and over, Carcinoma, Pancreatic Ductal mortality, Carcinoma, Pancreatic Ductal surgery, Cell Line, Tumor, Cohort Studies, Comparative Genomic Hybridization, DNA Copy Number Variations, DNA Mutational Analysis, Dipeptidases metabolism, Disease-Free Survival, Female, Genes, Tumor Suppressor, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Pancreatic Neoplasms mortality, Pancreatic Neoplasms surgery, Prognosis, Proportional Hazards Models, Proto-Oncogene Proteins genetics, Proto-Oncogene Proteins p21(ras), Tumor Suppressor Protein p53 genetics, ras Proteins genetics, Carcinoma, Pancreatic Ductal genetics, Chromosome Deletion, Chromosomes, Human, Pair 18 genetics, Dipeptidases genetics, Pancreatic Neoplasms genetics
Abstract

Purposes: Pancreatic cancer is the fourth leading cause of cancer-related death, and studies on the clinical relevance of its genomic imbalances are warranted., Experimental Design: Recurrent copy number alterations of cytobands and genes were analyzed by array comparative genomic hybridization (aCGH) in 44 resected pancreatic cancer specimens. Prognostic markers identified by aCGH were validated by PCR gene copy number assay in an independent validation cohort of 61 resected pancreatic cancers. The functions of gene identified were evaluated by proliferation, cell cycle, and migration assays in pancreatic cancer cells., Results: We showed recurrent copy number gains and losses in the first cohort. Loss of 18q22.3 was significantly associated with short-term overall survival in the first cohort (P = 0.019). This cytoband includes the carboxypeptidase of glutamate-like (CPGL) gene. CPGL gene deletion was associated with shorter overall survival in the validation cohort (P = 0.003). CPGL deletion and mutations of TP53 or Kras seem to be independent events. A Cox model analysis of the two cohorts combined showed that loss of 18q22.3/deletion of the CPGL gene was an independent poor prognostic factor for overall survival (HR = 2.72, P = 0.0007). Reconstitution of CPGL or its splicing variant CPGL-B into CPGL-negative pancreatic cancer cells attenuated cell growth, migration, and induced G(1) accumulation., Conclusion: Loss of 18q22.3/deletion of the CPGL gene is a poor prognostic marker in resected pancreatic cancer, and functional studies suggest the CPGL gene as growth suppressor gene in pancreatic cancer., (©2011 AACR.)

Published
2012
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