Search

Your search keyword '"ten Hagen, T. L. M."' showing total 42 results
Start Over Author "ten Hagen, T. L. M."
42 results on '"ten Hagen, T. L. M."'

7. SMAD4 exerts a tumor-promoting role in hepatocellular carcinoma

Author

Hernanda, P Y, primary, Chen, K, additional, Das, A M, additional, Sideras, K, additional, Wang, W, additional, Li, J, additional, Cao, W, additional, Bots, S J A, additional, Kodach, L L, additional, de Man, R A, additional, Ijzermans, J N M, additional, Janssen, H L A, additional, Stubbs, A P, additional, Sprengers, D, additional, Bruno, M J, additional, Metselaar, H J, additional, ten Hagen, T L M, additional, Kwekkeboom, J, additional, Peppelenbosch, M P, additional, and Pan, Q, additional

Published
2014
Full Text
View/download PDF

8. Isolated hypoxic hepatic perfusion (IHHP) using balloon catheter techniques : from laboratory to the clinic towards a percutaneous procedure

Author

Eggermont, A. M. M., Ijken, M. G. A., Etten, B., Sijp, J. R. M., Ten Hagen, T. L. M., Wiggers, T., Matthijs Oudkerk, Boeck, G., Bruijn, E. A., and Surgery

Subjects
Human medicine
Abstract

Background/Aims: The success of ana our extensive experience with TNF alpha-based isolated limb perfusions in patients with unresectable extremity soft tissue sarcomas made us explore the possibilities for a similar approach for the treatment of hepatic metastases. After experience with the classic surgical isolated hepatic perfusion in pigs and in patients, we concluded that the classic surgical approach was associated with serious drawbacks i.e., magnitude of the procedure with morbidity, lack of repeatability of the procedure, complexity and costs. These problems were addressed in a program aimed at developing a repeatable method of isolated perfusion of the liver with minimally invasive techniques. Methodology: We validated the methodology of isolated hypoxic hepatic perfusion using balloon catheter techniques in pigs. Results: The excellent pharmacokinetic profile of the procedure, resulting in very high regional drug concentrations and negligible systemic drug concentrations, allowed us to move on to the clinic and start to study and further develop this method in a phase I-II study using the drug melphalan, in patients with irresectable hepatic metastases. Conclusions: We aim to develop step by step a fully percutaneous approach for isolated hypoxic hepatic perfusion.

Published
2000

10. Enhancement of nonspecific resistance by liposome-encapsulated immunomodulators does not affect skin graft rejection in mice

Author

Ten Hagen, T. L. M., Ann Vossen, Vianen, W. V., Tibbe, G. J. M., Savelkoul, H. F. J., Heremans, H., and Bakker-Woudenberg, I. A. J. M.

Subjects
Life Science
Abstract

Administration of liposome-encapsulated immunomodulating agents muramyl tripeptide phosphatidyl ethanolamine (LE-MTPPE) or interferon-gamma (LE-IFN-gamma), or co-encapsulated MTPPE and IFN-gamma (LE-(MTPPE/IFN-gamma)) resulted in a dramatic increase of the nonspecific antimicrobial resistance in mice, as shown before. This kind of treatment is especially of use in immunocompromised hosts who are prone to severe infections. Application of these immunomodulators might protect these patients, e.g., transplant recipients, from opportunistic infections. However, accelerated rejection of the graft, resulting from augmentation of the antimicrobial defense in a nonspecific way, has to be avoided. In this study, the effect of treatment with LE-MT-PPE, LE-IFN-gamma, or LE-(MTPPE/IFN-gamma) on skin graft rejection in mice was investigated. It was found that prophylactic treatment of skin-grafted mice with immunomodulating formulations did not influence rejection of the graft. Moreover, in T cell-depleted mice, which showed a prolonged graft survival compared with immunocompetent recipients, the administration of immunomodulators did not change the survival time of the grafts compared with T cell-depleted mice that did not receive immunomodulators. The results clearly show that, in this experimental setting, application of the antimicrobial resistance-enhancing formulations (LE-MTPPE, LE-IFN-gamma, and LE-(MTPPE/IFN-gamma)) is allowed in graft-bearing recipients, without influencing graft survival.

Published
1995

11. Degree of tumour vascularity correlates with drug accumulation and tumour response upon TNF-alpha-based isolated hepatic perfusion

Author

van Etten, B, de Vries, M R, van IJken, M G A, Lans, T E, Guetens, G, Ambagtsheer, G, van Tiel, S T, de Boeck, G, de Bruijn, E A, Eggermont, A M M, ten Hagen, T L M, van Etten, B, de Vries, M R, van IJken, M G A, Lans, T E, Guetens, G, Ambagtsheer, G, van Tiel, S T, de Boeck, G, de Bruijn, E A, Eggermont, A M M, and ten Hagen, T L M

Abstract

Isolated hepatic perfusion (IHP) with melphalan with or without tumour necrosis factor alpha (TNF-alpha) is currently performed in clinical trials in patients with hepatic metastases. Previous studies led to the hypothesis that the use of TNF-alpha in isolated limb perfusion causes specific destruction of tumour endothelial cells and thereby induces an increased permeability of tumour vasculature. However, whether TNF-alpha contributes to the therapeutic efficacy in IHP still remains unclear. In an in vivo rat liver metastases model we studied three different tumours: colon carcinoma CC531, ROS-1 osteosarcoma and BN-175 soft-tissue sarcoma which exhibit different degrees of vascularisation. IHP was performed with melphalan with or without the addition of TNF-alpha. IHP with melphalan alone resulted, in all tumour types, in a decreased growth rate. However in the BN-175 tumour addition of TNF-alpha resulted in a strong synergistic effect. In the majority of the BN-175 tumour-bearing rats, a complete response was achieved. In vitro cytoxicity studies showed no sensitivity (CC531 and BN-175) or only minor sensitivity (ROS-1) to TNF-alpha, ruling out a direct interaction of TNF-alpha with tumour cells. The response rate in BN-175 tumour-bearing rats when TNF-alpha was coadministrated with melphalan was strongly correlated with drug accumulation in tumour tissue, as only in these rats a five-fold increased melphalan concentration was observed. Secondly, immunohistochemical analysis of microvascular density (MVD) of the tumour showed a significantly higher MVD for BN-175 tumour compared to CC531 and ROS-1. These results indicate a direct relation between vascularity of the tumour and TNF-alpha mediated effects. Assessment of the tumour vasculature of liver metastases would be a way of establishing an indication for the utility of TNF-alpha in this setting.

Published
2003

17. Poster Abstracts

Author

Littger, Ralf, primary, Alke, Alexandra, additional, Tewes, Bernhard, additional, Gropp, Felix, additional, Asai, T., additional, Watanabe, K., additional, Kuromi, K., additional, Kurohane, K., additional, Ogino, K., additional, Taki, T., additional, Tsukada, H., additional, Nakayama, J., additional, Oku, N., additional, Babai, I., additional, Matyas, G., additional, Baranji, L., additional, Milosevits, J., additional, Alving, C. R., additional, Bendas, G., additional, Rothe, U., additional, Scherphof, G. L., additional, Kamps, J. A. A. M., additional, Kessner, S., additional, Carafa, M., additional, Di Stefano, A., additional, Sozio, P., additional, Cacciatore, I., additional, Mosciatti, B., additional, Santucci, E., additional, Choice, E., additional, Harvie, P., additional, Galbraith, T., additional, Zunder, E., additional, Dutzar, B., additional, Anklesaria, P., additional, Paul, R., additional, Cocquyt, J., additional, De Cuyper, M., additional, Van der Meeren, P., additional, Cruz, M. E. M., additional, Gaspar, M. M., additional, Silva, M. T., additional, Dathe, M., additional, Nikolenko, H., additional, Wessolowski, A., additional, Schmieder, P., additional, Beyermann, M., additional, Bienert, M., additional, Santos, N. Dos, additional, Cox, K. A., additional, Allen, C., additional, Gallagher, R. C., additional, Ickenstein, L., additional, Mayer, L. D., additional, Bally, M. B., additional, Fischer, S., additional, Margalit, R., additional, Freisleben, H.-J., additional, Garidel, P., additional, Chen, H. C., additional, Moore, D., additional, Mendelsohn, R., additional, Keller, M., additional, Hildebrand, A., additional, Blume, A., additional, Girão da Cruz, M. T., additional, Simões, S., additional, Pedroso de Lima, M. C., additional, Graser, A., additional, Nahde, T., additional, Fahr, A., additional, Müller, R., additional, Müller-Brüsselbach, S., additional, Cudmore, S., additional, O'Mahony, D., additional, Hoving, S., additional, van Tiel, S. T., additional, Seynhaeve, A. L. B., additional, Ambagtsheer, G., additional, Eggermont, A. M. M., additional, ten Hagen, T. L. M., additional, Høyrup, P., additional, Jensen, S. S., additional, Jørgensen, K., additional, Iden, D., additional, Kuang, H., additional, Mullen, P., additional, Jacobs, C., additional, Roben, P., additional, Stevens, T., additional, Lollo, C., additional, Ishida, T., additional, Maeda, R., additional, Masuda, K., additional, Ichihara, M., additional, Kiwada, H., additional, Jung, K., additional, Reszka, R., additional, Kaiser, N., additional, Ohloff, I., additional, Linser-Haar, S., additional, Massing, U., additional, Schubert, R., additional, Kan, P., additional, Tsao, C. W., additional, Chen, W. K., additional, Wang, A. J., additional, Kimpfler, A., additional, Gerber, C., additional, Wieschollek, A., additional, Bruchelt, G., additional, Kobayashi, T., additional, Okada, Y., additional, Sone, S., additional, Harashima, H., additional, Maruyama, K., additional, Kondo, Masayo, additional, Lee, Chun Man, additional, Tanaka, Toshiyuki, additional, Su, Wei, additional, Kitagawa, Toru, additional, Ito, Toshinori, additional, Matsuda, Hikaru, additional, Murai, Toshiyuki, additional, Miyasaka, Masayuki, additional, Junji, Kimura, additional, Kondo, Masami, additional, Asai, Tomohiro, additional, Ogino, Koichi, additional, Taki, Takao, additional, Tsukada, Hideo, additional, Baba, Kazuhiko, additional, Oku, Naoto, additional, Koning, G. A., additional, Wauben, M. H. M., additional, Vestweber, D., additional, Everts, M., additional, Kok, R. J., additional, Schraa, A. J., additional, Molema, G., additional, Schiffelers, R. M., additional, Storm, G., additional, Kristl, J., additional, Šentjurc, M., additional, Abramović, Z., additional, Landry, S., additional, Perron, S., additional, Bestman-Smith, J., additional, Désormeaux, A., additional, Tremblay, M. J., additional, Bergeron, M. G., additional, Madeira, C., additional, Loura, L. M. S., additional, Fedorov, A., additional, Prieto, M., additional, Aires-Barros, M. R., additional, Marques, C. M., additional, Simões, S. I., additional, Cruz, M. E., additional, Cevc, G., additional, Martins, M. B., additional, Moreira, J. N., additional, Gaspar, R., additional, Allen, T. M., additional, Esposito, C., additional, Ortaggi, G., additional, Bianco, A., additional, Bonadies, F., additional, Malizia, D., additional, Napolitano, R., additional, Cametti, C., additional, Mossa, G., additional, Endert, Gerold, additional, Essler, Frank, additional, Lutz, Silke, additional, Panzner, Steffen, additional, Pastorino, F., additional, Brignole, C., additional, Pagnan, G., additional, Moase, E. H., additional, Ponzoni, M., additional, Pavelic, Z., additional, Škalko-Basnet, N., additional, Jalšenjak, I., additional, Penacho, N., additional, Pisano, C., additional, Bucci, F., additional, Serafini, S., additional, Martinelli, R., additional, Cupelli, A., additional, Marconi, A., additional, Ferrara, F. F., additional, Santaniello, M., additional, Critelli, L., additional, Tinti, O., additional, Luisi, P., additional, Carminati, P., additional, Galletti, B., additional, Sauer, I., additional, Schleef, M., additional, Voß, C., additional, Schmidt, T., additional, Flaschel, E., additional, König, S., additional, Wenger, T., additional, Dumond, J., additional, Bogetto, N., additional, Reboud-Ravaux, M., additional, Schramm, H. J., additional, Schramm, W., additional, Sheynis, T., additional, Rozner, S., additional, Kolusheva, S., additional, Satchell, D., additional, Jelnik, R., additional, Shigeta, Y., additional, Imanaka, H., additional, Ando, H., additional, Makino, T., additional, Baba, N., additional, Shimizu, K., additional, Takada, M., additional, Baba, K., additional, Namba, Y., additional, Simberg, Dmitri, additional, Danino, Dganit, additional, Talmon, Yeshayahu, additional, Minsky, Abraham, additional, Ferrari, Marilyn E., additional, Wheeler, Carl J., additional, Barenholz, Yechezkel, additional, Takada, Miki, additional, Shimizu, Kosuke, additional, Kuromi, Koici, additional, Takeuchi, Y., additional, North, J. R., additional, Nango, M., additional, Tewes, B., additional, Köchling, T., additional, Deissler, M., additional, Kühl, C., additional, Marx, U., additional, Strote, G., additional, Gropp, F., additional, Qualls, Marquita M., additional, Kim, Jong-Mok, additional, Thompson, David H., additional, Zhang, Zhi-Yi, additional, Shum, Pochi, additional, Collier, Joel H., additional, Hu, Bi-Huang, additional, Ruberti, Jeffrey W., additional, Messersmith, Phillip B., additional, Tsuruda, T., additional, Nakade, A., additional, Sadzuka, Y., additional, Hirota, S., additional, Sonobe, T., additional, Vorauer-Uhl, K., additional, Wagner, A., additional, Katinger, H., additional, Weeke-Klimp, A. H., additional, Bartsch, M., additional, Meijer, D. K. F., additional, Zeisig, R., additional, Walther, W., additional, Reß, A., additional, Fichtner, I., additional, Zschörnig, O., additional, Schiller, J., additional, Süß, M., additional, Bergmeier, C., additional, Arnold, K., additional, Nchinda, Godwin, additional, Überla, Klaus, additional, and Zschörnig, Olaf, additional

Published
2003
Full Text
View/download PDF

18. Oral Presentations—Abstracts

Author

Bartsch, M., primary, Meijer, D. K. F., additional, Scherphof, G. L., additional, Kamps, J. A. A. M., additional, Erdoğan, S., additional, Özer, A. Y., additional, Caner, B., additional, Bilgili, H., additional, Ickenstein, L. M., additional, Edwards, K., additional, Karlsson, G., additional, Mayer, L. D., additional, Eley, Crispin G. S., additional, Hu, Ning, additional, Jensen, Gerard M., additional, Kawahara, K., additional, Sekiguchi, A., additional, Kiyoki, E., additional, Morimoto, K., additional, Boerman, O. C., additional, Miyajima, M., additional, Kimura, J., additional, Koning, G. A., additional, Morselt, H. W. M., additional, Metselaar, Josbert M., additional, Wauben, Marca H. M., additional, Boerman, Otto C., additional, van Lent, Peter L., additional, Storm, Gert, additional, Pastorino, F., additional, Brignole, C., additional, Marimpietri, D., additional, Moase, E. H., additional, Allen, T. M., additional, Ponzoni, M., additional, Romøren, K., additional, Thu, B. J., additional, Evensen, Ø, additional, Rossi, S., additional, Ristori, S., additional, Martini, G., additional, Schiffelers, R. M., additional, Molema, G., additional, ten Hagen, T. L. M., additional, Janssen, A. P. C. A., additional, Ebben, R. G., additional, Schraa, A. J., additional, Kok, R. J., additional, Koning, G., additional, Storm, G., additional, Simões, S. I., additional, Marques, C. M., additional, Cruz, M. E., additional, Cevc, G., additional, Martins, M. B., additional, Summers, D., additional, Ruff, D., additional, Smalling, R. W., additional, Cardoza, D., additional, Dottavio, D., additional, Lasic, D., additional, Szebeni, J., additional, Baranyi, L., additional, Savay, S., additional, Milosevits, J., additional, Bunger, R., additional, Laverman, P., additional, Metselaar, J. M., additional, Chanan-Khan, A., additional, Liebes, L., additional, Muggia, F. M., additional, Cohen, R., additional, Barenholz, Y., additional, Alving, C. R., additional, Hoving, S., additional, Seynhaeve, A. L. B., additional, van Tiel, S. T., additional, Eggermont, A. M. M., additional, Tokutomi, K., additional, Sadzuka, Y., additional, Igarashi, A., additional, Konno, H., additional, and Sonobe, T., additional

Published
2003
Full Text
View/download PDF

28. Poster Abstracts

Author

Littger, Ralf, Alke, Alexandra, Tewes, Bernhard, Gropp, Felix, Asai, T., Watanabe, K., Kuromi, K., Kurohane, K., Ogino, K., Taki, T., Tsukada, H., Nakayama, J., Oku, N., Babai, I., Matyas, G., Baranji, L., Milosevits, J., Alving, C. R., Bendas, G., Rothe, U., Scherphof, G. L., Kamps, J. A. A. M., Kessner, S., Rothe, U., Bendas, G., Carafa, M., Di Stefano, A., Sozio, P., Cacciatore, I., Mosciatti, B., Santucci, E., Choice, E., Harvie, P., Galbraith, T., Zunder, E., Dutzar, B., Anklesaria, P., Paul, R., Cocquyt, J., De Cuyper, M., Van der Meeren, P., Cruz, M. E. M., Gaspar, M. M., Silva, M. T., Dathe, M., Nikolenko, H., Wessolowski, A., Schmieder, P., Beyermann, M., Bienert, M., Santos, N. Dos, Cox, K. A., Allen, C., Gallagher, R. C., Ickenstein, L., Mayer, L. D., Bally, M. B., Fischer, S., Margalit, R., Freisleben, H.-J., Garidel, P., Chen, H. C., Moore, D., Mendelsohn, R., Garidel, P., Keller, M., Hildebrand, A., Blume, A., Girão da Cruz, M. T., Simões, S., Pedroso de Lima, M. C., Graser, A., Nahde, T., Fahr, A., Müller, R., Müller-Brüsselbach, S., Harvie, P., Dutzar, B., Choice, E., Cudmore, S., O'Mahony, D., Anklesaria, P., Paul, R., Hoving, S., van Tiel, S. T., Seynhaeve, A. L. B., Ambagtsheer, G., Eggermont, A. M. M., ten Hagen, T. L. M., Høyrup, P., Jensen, S. S., Jørgensen, K., Iden, D., Kuang, H., Mullen, P., Jacobs, C., Roben, P., Stevens, T., Lollo, C., Ishida, T., Maeda, R., Masuda, K., Ichihara, M., Kiwada, H., Jung, K., Reszka, R., Kaiser, N., Ohloff, I., Linser-Haar, S., Massing, U., Schubert, R., Kan, P., Tsao, C. W., Chen, W. K., Wang, A. J., Kimpfler, A., Gerber, C., Wieschollek, A., Bruchelt, G., Schubert, R., Kobayashi, T., Okada, Y., Ishida, T., Sone, S., Harashima, H., Maruyama, K., Kiwada, H., Kondo, Masayo, Lee, Chun Man, Tanaka, Toshiyuki, Su, Wei, Kitagawa, Toru, Ito, Toshinori, Matsuda, Hikaru, Murai, Toshiyuki, Miyasaka, Masayuki, Junji, Kimura, Kondo, Masami, Asai, Tomohiro, Ogino, Koichi, Taki, Takao, Tsukada, Hideo, Baba, Kazuhiko, Oku, Naoto, Koning, G. A., Wauben, M. H. M., ten Hagen, T. L. M., Vestweber, D., Everts, M., Kok, R. J., Schraa, A. J., Molema, G., Schiffelers, R. M., Storm, G., Kristl, J., Šentjurc, M., Abramovi, Z., Landry, S., Perron, S., Bestman-Smith, J., Désormeaux, A., Tremblay, M. J., Bergeron, M. G., Madeira, C., Loura, L. M. S., Fedorov, A., Prieto, M., Aires-Barros, M. R., Marques, C. M., Simões, S. I., Cruz, M. E., Cevc, G., Martins, M. B., Moreira, J. N., Gaspar, R., Allen, T. M., Esposito, C., Ortaggi, G., Bianco, A., Bonadies, F., Malizia, D., Napolitano, R., Cametti, C., Mossa, G., Endert, Gerold, Essler, Frank, Lutz, Silke, Panzner, Steffen, Pastorino, F., Brignole, C., Pagnan, G., Moase, E. H., Allen, T. M., Ponzoni, M., Pavelic, Z., Škalko-Basnet, N., Jalšenjak, I., Penacho, N., Simões, S., Pedroso de Lima, M. C., Pisano, C., Bucci, F., Serafini, S., Martinelli, R., Cupelli, A., Marconi, A., Ferrara, F. F., Santaniello, M., Critelli, L., Tinti, O., Luisi, P., Carminati, P., Santaniello, M., Bucci, F., Tinti, O., Pisano, C., Critelli, L., Galletti, B., Luisi, P., Carminati, P., Sauer, I., Nikolenko, H., Dathe, M., Schleef, M., Voß, C., Schmidt, T., Flaschel, E., König, S., Wenger, T., Dumond, J., Bogetto, N., Reboud-Ravaux, M., Schramm, H. J., Schramm, W., Sheynis, T., Rozner, S., Kolusheva, S., Satchell, D., Jelnik, R., Shigeta, Y., Imanaka, H., Ando, H., Makino, T., Kurohane, K., Oku, N., Baba, N., Shimizu, K., Asai, T., Takada, M., Baba, K., Namba, Y., Oku, N., Simberg, Dmitri, Danino, Dganit, Talmon, Yeshayahu, Minsky, Abraham, Ferrari, Marilyn E., Wheeler, Carl J., Barenholz, Yechezkel, Takada, Miki, Shimizu, Kosuke, Kuromi, Koici, Asai, Tomohiro, Baba, Kazuhiko, Oku, Naoto, Takeuchi, Y., Kurohane, K., North, J. R., Namba, Y., Nango, M., Oku, N., Tewes, B., Köchling, T., Deissler, M., Kühl, C., Marx, U., Strote, G., Gropp, F., Qualls, Marquita M., Kim, Jong-Mok, Thompson, David H., Zhang, Zhi-Yi, Shum, Pochi, Collier, Joel H., Hu, Bi-Huang, Ruberti, Jeffrey W., Messersmith, Phillip B., Thompson, David H., Tsuruda, T., Nakade, A., Sadzuka, Y., Hirota, S., Sonobe, T., Vorauer-Uhl, K., Wagner, A., Katinger, H., Wagner, A., Vorauer-Uhl, K., Katinger, H., Weeke-Klimp, A. H., Bartsch, M., Meijer, D. K. F., Scherphof, G. L., Kamps, J. A. A. M., Zeisig, R., Walther, W., Reß, A., Fichtner, I., Zschörnig, O., Schiller, J., Süß, M., Bergmeier, C., Arnold, K., Nchinda, Godwin, Überla, Klaus, and Zschörnig, Olaf

Abstract

DOCSPER—A Synthetic Lipid Fit for In Vivo ApplicationDOCSPER [1,3-Dioleoyloxy-2-(N5-carbamoyl-spermine)-propane] is a cationic amphiphile consisting of a hydrophobic 1,3 dioleylglycerol moiety and threefold positively charged spermine head group (1). We optimised the 5-step-synthesis of the lipospermine and after up-scaling we have obtained sufficient amounts to initiate preclinical investigations. DOCSPER was tested for its ability to transfect eukaryotic cells in vitro. It has proven to possess high transfection efficiency in comparison to commercially available liposomal transfection agents. Furthermore, DOCSPER was extensively tested in several in vivo studies (23). These studies revealed a high transfection efficiency, whereas very low toxicity levels were detected. Thus, the results clearly indicate that the cationic lipid DOCSPER is a reliable, low-risk system for broad applications in gene therapy.Groth D. et al. Int J Pharm 1998; 162:143–157.Nikol S. et al. Int J Angiol 2000; 9:87–95.Armeanu S. et al. Mol Ther 2000; 1(4):366–375.

Published
1982
Full Text
View/download PDF

29. Oral Presentations—Abstracts

Author

Bartsch, M., Meijer, D. K. F., Scherphof, G. L., Kamps, J. A. A. M., Erdoan, S., Özer, A. Y., Caner, B., Bilgili, H., Ickenstein, L. M., Edwards, K., Karlsson, G., Mayer, L. D., Eley, Crispin G. S., Hu, Ning, Jensen, Gerard M., Kawahara, K., Sekiguchi, A., Kiyoki, E., Morimoto, K., Boerman, O. C., Miyajima, M., Kimura, J., Koning, G. A., Kimura, J., Morselt, H. W. M., Kamps, J. A. A. M., Scherphof, G. L., Metselaar, Josbert M., Wauben, Marca H. M., Boerman, Otto C., van Lent, Peter L., Storm, Gert, Pastorino, F., Brignole, C., Marimpietri, D., Moase, E. H., Allen, T. M., Ponzoni, M., Romøren, K., Thu, B. J., Evensen, Ø, Rossi, S., Karlsson, G., Ristori, S., Martini, G., Edwards, K., Schiffelers, R. M., Molema, G., Molema, G., ten Hagen, T. L. M., Janssen, A. P. C. A., Ebben, R. G., Schraa, A. J., Kok, R. J., Koning, G., Storm, G., Simões, S. I., Marques, C. M., Cruz, M. E., Cevc, G., Martins, M. B., Summers, D., Ruff, D., Smalling, R. W., Cardoza, D., Dottavio, D., Lasic, D., Szebeni, J., Baranyi, L., Savay, S., Milosevits, J., Bunger, R., Laverman, P., Metselaar, J. M., Storm, G., Chanan-Khan, A., Liebes, L., Muggia, F. M., Cohen, R., Barenholz, Y., Alving, C. R., ten Hagen, T. L. M., Hoving, S., Seynhaeve, A. L. B., van Tiel, S. T., Eggermont, A. M. M., Tokutomi, K., Sadzuka, Y., Igarashi, A., Konno, H., and Sonobe, T.

Abstract

Targeted Delivery of Antisense Oligodeoxynucleotides In Vivo by Means of Coated Cationic LipoplexesEarlier we reported on the massive uptake of liposomes surface-modified with negatively charged aconitylated albumin (Aco-HSA) by liver endothelial cells (EC) in vivo. In the present work we apply this principle for in vivo delivery of antisense oligodeoxynucleotides (ODN) to these cells by means of coated cationic lipoplexes (CCL) (1). CCL were prepared by complexing ODN with the cationic lipid DOTAP and subsequent coating of the complex by neutral lipids including a lipid-anchored poly(ethylene glycol). Aco-HSA was covalently coupled.The Aco-HSA-CCLs were 160 nm in size, contained 1.03 ± 0.35 nmol ODN and 54 ± 18 µg Aco-HSA per µ mol total lipid. The Aco-HSA-CCLs were rapidly eliminated from plasma, 60 of the injected dose being recovered in the liver after 30 m. Within the liver, the EC accounted for two thirds of total liver uptake. Non-targeted CCLs were eliminated very slowly: after 30 m >90 of the particles was in the blood. Currently, we compare the encapsulation efficiency, stability and targetability of the CCL with stabilized antisense lipid particles (SALP) (2), while also the biological activity of these carriers is addressed. In conclusion our results demonstrate that antisense ODN can be targeted very efficiently to EC in vivo, employing plasma-stable CCL, surface modified with negatively charged albumin.ReferencesStuart DD, Allen TM. BBA 2000; 1463:219–229.Semple S. et al. BBA 2001; 1510: 152–166.

Published
1982
Full Text
View/download PDF

31. Hyperthermia and smart drug delivery systems for solid tumor therapy.

Author

Seynhaeve ALB, Amin M, Haemmerich D, van Rhoon GC, and Ten Hagen TLM

Subjects
Antineoplastic Agents pharmacokinetics, Humans, Hyperthermia, Induced instrumentation, Nanoparticles chemistry, Neoplasms blood supply, Neoplasms physiopathology, Temperature, Thermometry, Time Factors, Tumor Microenvironment physiology, Antineoplastic Agents administration & dosage, Drug Delivery Systems methods, Hyperthermia, Induced methods, Neoplasms drug therapy
Abstract

Chemotherapy is a cornerstone of cancer therapy. Irrespective of the administered drug, it is crucial that adequate drug amounts reach all cancer cells. To achieve this, drugs first need to be absorbed, then enter the blood circulation, diffuse into the tumor interstitial space and finally reach the tumor cells. Next to chemoresistance, one of the most important factors for effective chemotherapy is adequate tumor drug uptake and penetration. Unfortunately, most chemotherapeutic agents do not have favorable properties. These compounds are cleared rapidly, distribute throughout all tissues in the body, with only low tumor drug uptake that is heterogeneously distributed within the tumor. Moreover, the typical microenvironment of solid cancers provides additional hurdles for drug delivery, such as heterogeneous vascular density and perfusion, high interstitial fluid pressure, and abundant stroma. The hope was that nanotechnology will solve most, if not all, of these drug delivery barriers. However, in spite of advances and decades of nanoparticle development, results are unsatisfactory. One promising recent development are nanoparticles which can be steered, and release content triggered by internal or external signals. Here we discuss these so-called smart drug delivery systems in cancer therapy with emphasis on mild hyperthermia as a trigger signal for drug delivery., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2020
Full Text
View/download PDF

32. A moderate thermal dose is sufficient for effective free and TSL based thermochemotherapy.

Author

van Rhoon GC, Franckena M, and Ten Hagen TLM

Subjects
Antineoplastic Agents pharmacokinetics, Drug Liberation, Humans, Hyperthermia metabolism, Temperature, Tumor Microenvironment physiology, Antineoplastic Agents administration & dosage, Drug Delivery Systems methods, Hyperthermia, Induced methods, Liposomes chemistry, Neoplasms drug therapy
Abstract

Hyperthermia, i.e. heating the tumor to a temperature of 40-43 °C is considered by many a valuable treatment to sensitize tumor cells to radiotherapy and chemotherapy. In recent randomized trials the great potential of adding hyperthermia to chemotherapy was demonstrated for treatment of high risk soft tissue sarcoma: +11.4% 5 yrs. overall survival (OS) and for ovarian cancer with peritoneal involvement nearly +12 months OS gain. As a result interest in combining chemotherapy with hyperthermia, i.e. thermochemotherapy, is growing. Extensive biological research has revealed that hyperthermia causes multiple effects, from direct cell kill to improved oxygenation, whereby each effect has a specific temperature range. Thermal sensitization of the tumor cell for chemotherapy occurs for many drugs at temperatures ranging from 40 to 42 °C with little additional increase of sensitization at higher temperatures. Increasing perfusion/oxygenation and increased extravasation are two other important hyperthermia induced mechanisms. The combination of free drug and hyperthermia has not been found to increase tumor drug concentration. Hence, enhanced effectiveness of free drug will depend on the thermal sensitization of the tumor cells for the applied drug. In contrast to free drugs, experimental animal studies combining hyperthermia and thermo-sensitive liposomal (TSL) drugs delivery have demonstrated to result in a substantial increase of the drug concentration in the tumor. For TSL based chemotherapy, hyperthermia is critical to both increase perfusion and extravasation as well as to trigger TSL drug release, whereby the temperature controlled induction of a local high drug concentration in a highly permeable vessel is driving the enhanced drug uptake in the tumor. Increased drug concentrations up to 26 times have been reported in rodents. Good control of the tissue temperature is required to keep temperatures below 43 °C to prevent vascular stasis. Further, careful timing of the drug application relative to the start of heating is required to benefit optimal from the combined treatment. From the available experimental data it follows that irrespective whether chemotherapy is applied as free drug or using a thermal sensitive liposomal carrier, the optimal thermal dose for thermochemotherapy should be 40-42 °C for 30-60 min, i.e. equivalent to a CEM43 of 1-15 min. Timing is critical: most free drug should be applied simultaneous with heating, whereas TSL drugs should be applied 20-30 min after the start of hyperthermia., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2020
Full Text
View/download PDF

33. Expression and prognostic significance of thymidylate synthase (TS) in pancreatic head and periampullary cancer.

Author

van der Zee JA, van Eijck CH, Hop WC, van Dekken H, Dicheva BM, Seynhaeve AL, Koning GA, Eggermont AM, and Ten Hagen TL

Subjects
Adenocarcinoma therapy, Adult, Aged, Aged, 80 and over, Antimetabolites, Antineoplastic therapeutic use, Biomarkers, Tumor analysis, Chemoradiotherapy, Common Bile Duct Neoplasms therapy, Female, Fluorouracil therapeutic use, Humans, Male, Middle Aged, Pancreatic Neoplasms therapy, Prognosis, Adenocarcinoma enzymology, Ampulla of Vater, Common Bile Duct Neoplasms enzymology, Pancreatic Neoplasms enzymology, Thymidylate Synthase analysis
Abstract

Background: Pancreatic cancer has a dismal prognosis. Attempts have been made to improve outcome by several 5-FU based adjuvant treatment regimens. However, the results are conflicting. There seems to be a continental divide with respect to the use of 5-FU based chemoradiotherapy (CRT). Furthermore, evidence has been presented showing a different response of pancreatic head and periampullary cancer to 5-FU based CRT. Expression of thymidylate synthase (TS) has been associated with improved outcome following 5-FU based adjuvant treatment in gastrointestinal cancer. This prompted us to determine the differential expression and prognostic value of TS in pancreatic head and periampullary cancer., Patients and Methods: TS protein expression was studied by immunohistochemistry on original paraffin embedded tissue from 212 patients following microscopic radical resection (R0) of pancreatic head (n = 98) or periampullary cancer (n = 114). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS), and conventional prognostic factors., Results: High cytosolic TS expression was present in 26% of pancreatic head tumours and 37% of periampullary tumours (p = .11). Furthermore, TS was an independent factor predicting favourable outcome following curative resection of pancreatic head cancer (p = .003, .001 and .001 for RFS, CSS and OS, respectively). In contrast, in periampullary cancer, TS was not associated with outcome (all p > .10)., Conclusion: TS, was found to be poorly expressed in both pancreatic head and periampullary cancer and identified as an independent prognostic factor following curative resection of pancreatic head cancer., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Published
2012
Full Text
View/download PDF

34. Tumour basement membrane laminin expression predicts outcome following curative resection of pancreatic head cancer.

Author

van der Zee JA, van Eijck CH, Hop WC, Biermann K, Dicheva BM, Seynhaeve AL, Koning GA, Eggermont AM, and Ten Hagen TL

Subjects
Adenocarcinoma metabolism, Adenocarcinoma pathology, Adult, Aged, Aged, 80 and over, Collagen Type IV metabolism, Disease-Free Survival, Female, Humans, Male, Middle Aged, Predictive Value of Tests, Prognosis, Randomized Controlled Trials as Topic, Retrospective Studies, Basement Membrane metabolism, Basement Membrane pathology, Carcinoma, Pancreatic Ductal metabolism, Carcinoma, Pancreatic Ductal pathology, Laminin biosynthesis, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology
Abstract

Background: Although widely fragmented BMs have been associated with adverse outcome in several cancer types, comparatively little is known with respect to its effect on the prognosis of pancreatic cancer. The aim of the current study was therefore to determine the prognostic value of tumour basement membrane (BM) continuity in two anatomically closely related, however, prognostically different tumours, pancreatic head- and periampullary cancer., Methods: Tumour BM continuity was determined by immunohistochemical staining of its two major components, laminin and collagen type IV. Associations were made with recurrence free survival (RFS), cancer-specific survival (CSS), overall survival (OS) and conventional prognostic factors., Results: Fifty-nine and 61% of pancreatic head and periampullary tumours, respectively, showed limited BM laminin expression. Whereas 43% and 41% of pancreatic head and periampullary cancers, respectively, showed limited BM collagen type IV expression. Limited BM laminin was associated with poor outcome following curative resection of pancreatic head cancer (P=0.034, 0.013 and 0.017 for RFS, CSS and OS, respectively). Two and a half times as many patients with ≥ 25% BM laminin were recurrence free and alive 5 years following resection compared with those with limited BM laminin. Although staining patterns of both BM components were weakly correlated with each other, BM collagen type IV expression was not significantly associated with outcome in either tumour type., Conclusion: Discontinuous BMs, determined by laminin expression, are associated with poor outcome following curative resection of pancreatic head cancer.

Published
2012
Full Text
View/download PDF

35. Bio-chemotherapeutic strategies and the (dis) utility of hypoxic perfusion of liver, abdomen and pelvis using balloon catheter techniques.

Author

van Ijken MG, van Etten B, Brunstein F, ten Hagen TL, Guetens G, de Wilt JH, de Bruijn EA, and Eggermont AM

Subjects
Animals, Antineoplastic Agents adverse effects, Catheterization adverse effects, Chemotherapy, Cancer, Regional Perfusion adverse effects, Humans, Tumor Necrosis Factor-alpha administration & dosage, Tumor Necrosis Factor-alpha adverse effects, Abdominal Neoplasms drug therapy, Antineoplastic Agents administration & dosage, Catheterization methods, Chemotherapy, Cancer, Regional Perfusion methods, Liver Neoplasms drug therapy, Pelvic Neoplasms drug therapy
Abstract

Aims: To review the development and current status of balloon catheter mediated hypoxic perfusion of abdomen, pelvis and liver for treatment of locally advanced malignancies. Within this context we focus on the addition of tumour necrosis factor-alpha (TNF) to these minimal invasive perfusion procedures., Methods: A literature search on these topics was carried out in PubMed for indexed articles and in all issues of Regional Cancer Treatment. The findings were related to our own experiences., Results: Hypoxic abdominal (HAP) and hypoxic pelvic perfusion (HPP) using balloon catheters, are currently applied modalities for treatment of a wide variety of abdominal and pelvic tumours, yet scientific validation of these procedures is poor. Following the results of several Phase I-II trials, both treatments are associated with severe systemic toxicity, significant morbidity and even mortality. The degree of systemic leakage associated with these procedures prohibits addition of TNF. For leakage free liver perfusion surgery is still required, as with current balloon catheter techniques it is not possible to perform leakage free isolated hypoxic hepatic perfusion (IHHP), using either orthograde or retrograde hepatic flow. Experimental and clinical observations suggest that within any perfusion setting, the utilization of TNF is only indicated for treatment of highly vascularised tumours and not for treatment of colorectal tumours., Conclusion: Balloon catheter technology in its present form does not provide adequate leakage control in any of these settings and is therefore associated with considerable toxicity. It is associated with poor response rates and cannot be considered in any setting as a standard of care.

Published
2005
Full Text
View/download PDF

36. Balloon catheter hypoxic pelvic perfusion with mitomycin C and melphalan for locally advanced tumours in the pelvic region: a phase I-II trial.

Author

van Ijken MG, van Etten B, Guetens G, de Bruijn EA, Ten Hagen TL, Wiggers T, and Eggermont AM

Subjects
Adult, Aged, Antibiotics, Antineoplastic adverse effects, Antineoplastic Agents, Alkylating adverse effects, Feasibility Studies, Female, Humans, Magnetic Resonance Imaging, Male, Melphalan adverse effects, Middle Aged, Mitomycin adverse effects, Neoadjuvant Therapy, Neoplasm Staging, Pain Measurement, Pelvic Neoplasms radiotherapy, Pelvic Neoplasms surgery, Radiotherapy Dosage, Remission Induction, Survival Rate, Tomography, X-Ray Computed, Antibiotics, Antineoplastic therapeutic use, Antineoplastic Agents, Alkylating therapeutic use, Catheterization methods, Chemotherapy, Cancer, Regional Perfusion methods, Melphalan therapeutic use, Mitomycin therapeutic use, Pelvic Neoplasms drug therapy
Abstract

Aims: To investigate the feasibility of hypoxic pelvic perfusion (HPP), using balloon catheter techniques as treatment modality for locally advanced pelvic malignancies., Methods: In a phase I--II study, 16 patients with various non-resectable pelvic tumours were treated with two HPP with MMC and melphalan, followed by radiotherapy (25 Gy) and surgical resection if feasible. Toxicity and procedure related complications were documented. Tumour responses were assessed by MRI or CT. Pain reductive effects were assessed by evaluation of pain registration forms., Results: HPP resulted in augmented regional drug concentrations with relatively low systemic levels. Some severe systemic toxicity was observed. One procedure related death occurred. Pain reduction effects were short-lived. Ten patients had radiological NC, two PD and one PR. In 11 patients surgical resection was performed, which was microscopically radical in six cases. Mean survival was 26.8 months (range 1--86)., Conclusion: The seemingly favorable pharmacokinetic profiles observed with HPP in this and other studies can still lead to severe systemic toxicity. In terms of survival, local (re-)recurrence and pain reduction there seems no benefit of addition of HPP to pre-operative radiotherapy. HPP with MMC and melphalan, does not seem a therapeutic option in patients with locally advanced pelvic tumours.

Published
2005
Full Text
View/download PDF

37. Dynamic contrast-enhanced MRI using macromolecular contrast media for monitoring the response to isolated limb perfusion in experimental soft-tissue sarcomas.

Author

Preda A, Wielopolski PA, Ten Hagen TL, van Vliet M, Veenland JF, Ambagtsheer G, van Tiel ST, Vogel MW, Eggermont AM, Krestin GP, and van Dijke CF

Subjects
Animals, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Chemotherapy, Cancer, Regional Perfusion methods, Extremities blood supply, Macromolecular Substances, Male, Prognosis, Rats, Rats, Inbred BN, Treatment Outcome, Albumins, Contrast Media, Gadolinium DTPA, Image Enhancement methods, Magnetic Resonance Imaging methods, Melphalan administration & dosage, Sarcoma, Experimental diagnosis, Sarcoma, Experimental drug therapy, Tumor Necrosis Factor-alpha administration & dosage
Abstract

The objective of this study was to evaluate the potential of dynamic contrast-enhanced MRI for quantitative characterization of tumor microvessels and to assess the microvascular changes in response to isolated limb perfusion with TNF-alpha and melphalan. Dynamic contrast-enhanced MRI was performed in an experimental cancer model, using a macromolecular contrast medium, albumin-(Gd-DTPA)45. Small fragments of BN 175, a soft-tissue sarcoma, were implanted in 11 brown Norway (BN) rats. Animals were assigned randomly to a control (Haemaccel) or drug-treated group (TNF-alpha/melphalan). MRI was performed at baseline and 24 h after ILP. The transendothelial permeability (K(PS)) and the fractional plasma volume (fPV) were estimated from the kinetic analysis of MR data using a two-compartment bi-directional model. K(PS) and fPV decreased significantly in the drug-treated group compared to baseline (p<0.05). In addition, K(PS) post therapy was significantly lower (p<0.05) in the drug-treated group than in the control group. There was no significant difference in fPV between the drug-treated and the control group after therapy. Tumor microvascular changes in response to isolated limb perfusion can be determined after 24 h by dynamic contrast-enhanced MRI. The data obtained in this experimental model suggest possible applications in the clinical setting, using the appropriate MR contrast agents.

Published
2004
Full Text
View/download PDF

38. Balloon catheter hypoxic abdominal and pelvic perfusion with tumour necrosis factor-alpha, Melphalan and Mitomycin C: a pharmacokinetic study in pigs.

Author

van IJken MG, de Bruijn EA, ten Hagen TL, de Boeck G, van Eijck CH, and Eggermont AM

Subjects
Animals, Antineoplastic Agents analysis, Antineoplastic Agents pharmacokinetics, Balloon Occlusion methods, Hypoxia, Melphalan blood, Melphalan pharmacokinetics, Mitomycin blood, Mitomycin pharmacokinetics, Models, Animal, Swine, Tumor Necrosis Factor-alpha analysis, Tumor Necrosis Factor-alpha pharmacokinetics, Abdominal Neoplasms drug therapy, Antineoplastic Agents administration & dosage, Chemotherapy, Cancer, Regional Perfusion methods, Melphalan administration & dosage, Mitomycin administration & dosage, Pelvic Neoplasms drug therapy, Tumor Necrosis Factor-alpha administration & dosage
Abstract

Background: Addition of tumour necrosis factor-alpha (TNF) to hypoxic abdominal perfusion (HAP) and hypoxic pelvic perfusion (HPP) with chemotherapeutic agents for treatment of un-resectable malignancies may lead to similar enhanced anti-tumour effects as are observed when TNF is added to isolated limb perfusions (ILP) with Melphalan. Here, we validate the methodology of HAP and HPP using balloon catheter techniques, and investigate the distribution of TNF, Melphalan and Mitomycin C (MMC) over the regional and systemic blood compartments when applying these techniques., Materials and Methods: Twelve pigs underwent HAP or HPP with TNF, Melphalan and MMC for 20 min. Throughout and after the procedures blood samples were obtained from hepatic, portal and systemic blood compartments and plasma concentrations of perfused agents were determined., Results: We demonstrated that HAP and HPP result in temporary loco-regional concentration advantages of all perfused agents, although from start of perfusion significant systemic leakage occurred., Conclusion: On basis of these results it seems that the advantage in terms of regional plasma concentration of TNF may be insufficient for TNF-mediated effects to occur, making future addition of this cytokine to these procedures in the clinical setting questionable. The observed regional concentration advantages of MMC and Melphalan, however, warrant further studies on clinical application of these agents in both settings.

Published
2004
Full Text
View/download PDF

39. Balloon catheter hypoxic abdominal perfusion with Mitomycin C and Melphalan for locally advanced pancreatic cancer: a phase I-II trial.

Author

van IJken MG, van Etten B, Guetens G, ten Hagen TL, Jeekel J, de Bruijn EA, Eggermont AM, and van Eijck CH

Subjects
Aged, Balloon Occlusion methods, Female, Humans, Hypoxia, Infusions, Intra-Arterial methods, Male, Middle Aged, Pain drug therapy, Pain etiology, Pain Measurement, Pancreatic Neoplasms complications, Remission Induction, Treatment Outcome, Antineoplastic Agents administration & dosage, Chemotherapy, Cancer, Regional Perfusion methods, Melphalan administration & dosage, Mitomycin administration & dosage, Pancreatic Neoplasms drug therapy
Abstract

Background: Developments in balloon catheter methodology have made hypoxic abdominal perfusion (HAP) with anti-tumour agents possible with only minimal invasive surgery. The initial reports on this modality and celiac axis stop-flow infusion for treatment of pancreatic cancer were very promising in terms of tumour response, median survival and pain reduction. Recent reports, however, have not been able to confirm these results and some have disputed the efficacy of these currently still applied treatment modalities., Methods: Twenty-one patients with advanced pancreatic carcinoma were included in a phase I-II trial of HAP with MMC and Melphalan followed by celiac axis infusion (CAI) with the same agents six weeks later. Tumour response was assessed by abdominal-CT and by determining tumour markers. Effect on pain reduction was assessed by evaluation of pain registration forms., Results: HAP resulted in augmented regional drug concentrations. One patient died after CAI due to acute mesenterial ischaemia. One agent-toxicity related death was observed in the phase-I study. Significant hematological toxicity was observed after HAP and CAI at MTD. No patients were considered resectable after treatment. Median survival after HAP was 6 months (range 1-29). Pain reduction was experienced by only 5/18 patients and was short-lived., Conclusion: In contrast to earlier reports HAP and CAI with MMC and Melphalan did not demonstrate any benefit in terms of tumour response, median survival and pain reduction, compared to less invasive treatment options. As this treatment was associated with significant toxic side-effects and even one procedure related death, we do not consider this a therapeutic option in patients with advanced pancreatic cancer.

Published
2004
Full Text
View/download PDF

40. Involvement of endothelial monocyte activating polypeptide II in tumor necrosis factor-alpha-based anti-cancer therapy.

Author

Lans TE, Van Horssen R, Eggermont AM, and Ten Hagen TL

Subjects
Animals, Cytokines biosynthesis, Cytokines genetics, Cytokines pharmacology, Drug Synergism, Humans, Neoplasm Proteins biosynthesis, Neoplasm Proteins genetics, Neoplasm Proteins pharmacology, Neoplasms genetics, Neoplasms metabolism, RNA-Binding Proteins biosynthesis, RNA-Binding Proteins genetics, RNA-Binding Proteins pharmacology, Antineoplastic Agents pharmacology, Cytokines physiology, Neoplasm Proteins physiology, Neoplasms drug therapy, RNA-Binding Proteins physiology, Tumor Necrosis Factor-alpha pharmacology
Abstract

In 1990 Clauss et al. first reported on a 44-kDa polypeptide, later called Endothelial Monocyte Activating Polypeptide II (EMAP II). This protein was discovered in the supernatant of Meth-A fibrosarcoma cells and was shown to enhance the induction of the procoagulant Tissue Factor (TF) on endothelial cells. Besides up-regulation of TF mRNA, EMAP II increases cellular receptors for TNF on endothelial cells, which is likely to enhance the predisposition of tumors to undergo thrombosis and hemorrhagic necrosis, once challenged with TNF. This feature enables EMAP II to up-regulate the TNF sensitivity of TNF-resistant tumors, an observation of importance in developing new approaches aimed at improving the efficacy of TNF as an anticancer treatment. We describe the potential additional effects of EMAP II, when used in combination with TNF, with regards to antitumor activity in the Isolated Limb Perfusion (ILP) setting. In addition, we describe our experimental data in human sarcoma, which also supports this hypothesis.

Published
2004

41. Lack of efficacy of Doxil in TNF-alpha-based isolated limb perfusion in sarcoma-bearing rats.

Author

ten Hagen TL, Hoving S, Ambagtsheer G, van Tiel ST, and Eggermont AM

Subjects
Animals, Disease Models, Animal, Hindlimb drug effects, Hindlimb pathology, Humans, Male, Organ Culture Techniques, Rats, Antibiotics, Antineoplastic pharmacology, Chemotherapy, Cancer, Regional Perfusion, Doxorubicin pharmacology, Sarcoma drug therapy, Tumor Necrosis Factor-alpha pharmacology
Abstract

Here we show that Doxil has minimal antitumour activity in the isolated limb perfusion (ILP) setting and its activity was not enhanced by the addition of tumour necrosis factor (TNF). Doxil accumulation in tumour tissue was low and also not augmented by TNF. In contrast, activity of free conventional doxorubicin was enhanced by TNF. We conclude that application of Doxil in a TNF-based ILP is not a useful alternative to free conventional doxorubicin or melphalan.

Published
2004
Full Text
View/download PDF

42. Peptide-targeted PEG-liposomes in anti-angiogenic therapy.

Author

Janssen AP, Schiffelers RM, ten Hagen TL, Koning GA, Schraa AJ, Kok RJ, Storm G, and Molema G

Subjects
Angiogenesis Inhibitors therapeutic use, Animals, Carcinoma, Lewis Lung drug therapy, Carcinoma, Lewis Lung metabolism, Cells, Cultured, Drug Carriers, Endothelium, Vascular drug effects, Endothelium, Vascular metabolism, Flow Cytometry instrumentation, Flow Cytometry methods, Humans, In Vitro Techniques, Liposomes chemistry, Mice, Microscopy, Confocal instrumentation, Microscopy, Confocal methods, Neovascularization, Pathologic drug therapy, Peptide Fragments administration & dosage, Peptide Fragments chemistry, Receptors, Vascular Endothelial Growth Factor metabolism, Time Factors, Transplants, Angiogenesis Inhibitors administration & dosage, Drug Delivery Systems, Oligopeptides chemistry, Polyethylene Glycols chemistry
Abstract

Peptides with the RGD amino acid sequence show affinity for the alpha(v)beta(3) integrin, an integrin which is over-expressed on angiogenic endothelium and involved in cell adhesion. A peptide with the sequence ATWLPPR has been demonstrated to show affinity for the vascular endothelial growth factor (VEGF) receptor, a receptor involved in the proliferation of endothelial cells. By coupling these peptides to liposomes, these liposomes can serve as a site-specific drug delivery system to tumor endothelial cells in order to inhibit angiogenesis. In the present study we demonstrate that the coupling of cyclic RGD-peptides or ATWLPPR-peptides to the surface of PEG-liposomes results in binding of these liposomes to endothelial cells in vitro. Subsequent studies with RGD-peptide targeted liposomes in vivo also demonstrate specific binding to the tumor endothelium., (Copyright 2002 Elsevier Science B.V.)

Published
2003
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results