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4. Abstracts of poster presentations

Author

Agostinho, A. B., Rosi, F., Tabucchi, A., Carlucci, F., Pizzichini, M., Arnér, Elias S. J., Eriksson, Staffan, Barankiewicz, J., Trembacz, H., Zwierzchowski, L., Bergman, A. M., van Haperen, V. W. T. Ruiz, Veerman, G., Vermorken, J. B., Peters, G. J., Bory, C., Chantin, C., Rocca, J. L., Bzowska, A., Ananlev, A. V., Ramzaeva, N., Alksins, E., Maurins, J. A., Kulikowska, E., Shugar, D., Davies, P. M., Fairbanks, L. D., Simmonds, H. A., De Graaf, T. W., Van Dijk, W., de Jong D., Huysmans F., De Abreu R., Monnens L., Dijkman H., van Liebergen F., Assmann K., Duley, J. A., Hanefeld, F., Fabianowska-Majewska, K., Duley, A. J., Greger, J., Wasiak, T., Gathof, B. S., Ried, T., Zwieauer, K., Gresser, U., Griesmacher, A., Weigel, G., Müller, M. M., Gross, M., Empl, W., Guisan, B., Roch-Ramel, F., Harley, E. H., Baumgarten, I., Kaletha K., Nagel-Starczynowska G., Karlsson, Anna, Lambooy, L., Boerbooms, A., De Abreu, R., van de Putte, L., Stolk, J., vd Pulte, L., Komissarov, A. A., Romanova, D. V., Debabov, V. G., Kozlov, A. M., Sokolov, V. B., Aksinenko, A. Y., Fetisov, V. I., Komoriya, Keiji, Osada, Yoshio, Hasegawa, Masaichi, Kondo, Shiro, Couch, Ronald C., Griffin, Travis B., Lakaschus, G., Löffler, H. G., Löffler, M., Jiménez, M. López, Salinero, M. A., Guilarte, J. Sánchez, Matesanz, J. Perianes, Medina, L. Vigil, Galiana, J. Ruiz, Marlewski, M., Smolenski, R. T., Swierczynski, J., Rutkowski, B., Zydowo, M. M., Micheli, V., Pescaglini, M., Sestini, S., Jacomelli, G., Magagnoli, C., Pompucci, G., Hayek, G., Mimouni, M., Boptemps, F., Van den Berghe, G., Miranda, M. E., Mateos, F. A., Herrero, E., González, A., Puig, J. G., Miscetti, P., Minelli, A., Proietti, A., Moroni, M., Mezzasoma, I., Moro, J. F., Noam, I., Cameron, J. S., McBride, M. B., Mathew, C. G. P., Ogg, C. S., Puig, J. G., Miranda, M. E., Mateos, F. A., Luzi, L., Noordhuis, P., Kazemier, K., Kaspers, G. J. L., Overgaard-Hansen, K., Marcussen, M., Klenow, H., Pelatti, A., Quaratino, C. P., D'Amario, C., Tentarelli, R., Giacomello, A., Rocchigiani, M., Iacomelli, G., Pandolfi, M. L., Arezzini, L., Terzuoli, L., Pagani, R., Di Sciascio, N., Colosimo, A., Ranieri-Paggi, M., Ronca, F., Brown, P. E., Moir, A. J. G., Raggi, A., Schwendel A., Grune T., Siems W. G., Holzhuetter H. G., Sebesta, I., Krijt, J., Vondrak, K., Kmoch, S., Hrebicek, M., Senatore, G., Del Lucchese, G., Martini, C., Lucacchini, A., Siems, W. G., Mertsch, K., Blasig, I., Grune, T., Skladanowski, A. C., Hoffmann, C. S., Krass, J. D., Makarewicz, W., Jastorff, B., Slingerland, R. J., Bodlaender, J. M., Van Lenthe, H., Elzinga, L., Van Kuilenburg, A. B. P., Voûte, P. A., Van Gennip, A. H., Smid, K., van der Wilt, C. L., Aherne, G. W., Pinedo, H. M., Sorqi, M. L., Rucci, C., Zoppini, A., Staub M., Sasvári-Székely M., Spasokukockaja T., Hrabák A., Stolk, J. N., De Abreu, R. A., De Koning, D. G. M., Lambooy, L. H. M., Kerstens, P. J. S. M., Boerbooms, A. M. Th., van de Putte, L. B. A., Szüts, P., Szirovicza, éva, åbrahám, C. S., Havass, Z., Jezewska, M. M., Van Acker, K. J., Eyskens, F. J., Verkerk, R. H., Scharpé, S. S., van Kuppevelt, T. H., Veerkamp, J. H., Sabina, R. L., Van Laar J. A. M., Mayhew E., Durrani F. A., Peters G. J., Rustum Y. M., Wang, J. Z., Leoncini, R., Vannoni, D., and Marinello, E.

Published
1993
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5. Scientific Proceedings Second International Symposium on Cytostatic Drug Resistance

Author

Hill, Bridget T., Hosking, L. K., McClean, S., Shellard, S. A., Dempke, W. C. M., Whelan, R. D. H., Sehested, M., Friche, E., Demant, E. J. F., Jensen, P. B., Kopnin, B. P., Wolf, B., Seidel, A., Nickelsen, M., Brandt, I., Heinemann, G., Dietel, M., Bremer, S., Hoof, T., Tümmler, B., Broxterman, H. J., Versantvoort, C. H. M., Kuiper, C. M., Feller, N., Schuurhuis, G. J., Lankelma, J., Gupta, S., Tsuruo, T., Kim, C., Gollapudi, S., Bittl, A., Nap, M., Jäger, W., Lathan, B., Lang, N., Raikhlin, N. T., Perevozchikov, A. G., Volodina, J. L., Licht T., Fiebig H. H., Bross K. J., Herrmann F., Mertelsmann R., Bashir, I., Sikora, K., Foster, C. S., Castagna, M., Viacava, P., Cianfrigliao, M., Favati, A., Collecchi, P., Caligo, M. A., Cipollini, G., Bevilacqua, G., Schrenk, D., Gant, T. W., Silverman, J. A., Thorgeirsson, S. S., Harstrick, A., Zhang, Z. G., Schmoll, H. J., Rustum, Y., Mitze, M., Beck, T., Weikel, W., Brumm, C., Knapstein, P. G., McDonald, T., Gardner, P., Kang, N., van der Heyden, S. A. M., Elst, H. J., Stein, U., Jandrig, B., Krause, H., Schmidt-Peter, P., Frege, J., Wunderlich, V., Boven, E., van Kalken, C. K., Pinedo, H. M., Gebauer, W., Fallgren-Gebauer, E., Diete, M., Wagner, T., Müller, M. R., Lennartz, K., Nowrousian, H. R., Seeber, S., Shtil, A. A., Kazarov, A. R., Gudkov, A. V., Stavrovskaya, A. A., Djuraeva, F. H., Stromskaya, T. P., Noller, A., Frese, G., Neumann, M., Wilisch, A., Probst, H., Gekeler, V., Handgretinger, R., Schmidt, H., Muller, C. P., Dopfer, R., Klingebiel, T., Niethammer, D., Weger, S., Diddens, H., Daumiller, E., Bunge, A., Lilischkis, R., Salmassi, A., Kopun M., Scherthan H., Granzow C., Leuschner, I., Schmidt, D., Hoffmann, H., Harms, D., Scagliotli, G. V., Leonardo, E., Cappia, S., Esposito, G., Tombesi, M., Cianfriglia, M., Esposito, G. V., Merendino, N., Viora, M., Caserta, M., Tritarelli, E., Rocca, E., Boccoli, G., Samoggia, P., Fossati, C., Testa, U., Peschle, C., Darling, J. L., Ashmore, S. M., Peterson, D. C., Thomas, D. G. T., Kramer, R. A., Stanlunas, R., Summerhayes, T., Lion, T., Shoemaker, R. H., Wu, L., Smythe, A., Boyd, M. R., Beck, W. T., Danks, M. K., Wolverton, J. S., Chen, M., Bugg, B. Y., Suttle, D. P., Catapano, C. V., Fernandes, D. J., Gieseler, F., Boege, F., Erttmann, R., Arps, H., Zwelling, L., Wilms, K., Biersack, H., Kaspers, G. J. L., Pieters, R., Klumper, E., de Waal, F. C., van Wering, E. R., Veerman, A. J. P., Schmidt, C. A., Lorenz, F., Schäfer, A., Kirsch, A., Siegert, W., Huhn, D., Simon, W. E., Siebert, G., Schneider, M., Oettling, M., Reymann, A., Entmann, R., Schmidt, S., Woermann, C., Windmeier, C., Herzig, I., Schaefer, B., Heidebrecht, H. J., Wacker, H. H., Künnemann, H., van Heijningen, Th. H. M., Slovak, M. L., Baak, J. P. A., Steidtmann, K., Fichtinger-Schepman, A. -M. J., Hill, B. I., Scanlon, K. J., Zeller, W. J., Chen, G., Gietema, J. A., de Vries, E. G. E, Sleijfer, D.Th, Willemse, P. H. B., Guchelaar, H. J., Uges, D. R. A., Aulenbacher, P., Voegeli, R., Mulder, N. H., Skrezek, C., Bertermann, H., Eichholtz-Wirth, H., Born, R., Bier, H., Koch, M., Bernhardt, G., Hählen, K., Reile, H., van Zantwijk, C. H., Wering, E. R. van, Görögh, T., Lippert, B., Werner, J. A., Eickbohm, J. E., Mickiseh, G. H., Gottesman, M. M., Pastan, I., Hofmann, J., Wolf, A., Spitaler, M., Bock, G., Grunicke, H., Ponstingl, H., Roth, I., Granzow, C., Dörner, C., Erttmann, R., Looft, G., Ossenkoppele, G. J., Scheffer, G. L., Atassi, G., Pierre, A., Kraus, L., Leonce, S., Regnier, G., Dhainaut, A., Ponstingl H., Stöhr M., Rohlff, C., Glazer, R. I., Cho-Chung, Y. S., Höllt, V., Kouba, M., Vogt, G., Allmeier, H., Nissen, N. I., Cros, S., Guilbaud, N., Dunn, T., Berlion, M., Atassi, G., Bizzari, J. P., Messing, A. M., Matuschek, A., Mutter, I., Kiwit, J. C. W., Bastian, L., Goretzki, P. E., Frilling, A., Simon, D., Röher, H. D., Reichle, A., Altmayr, F., Rastetter, J., Erbil, C., Jaques, G., Maasberg, M., Havemann, K., Häußermann, K., Heidebrecht, H. -J., Van de Vrie, W., Gheuens, E. E. O., Durante, N. M. C., De Bruijn, E. A., Marquet, R. L., Van Oosterom, A. T., Eggermont, A. M. M., Stow, M. W., Vickers, S. E., Warr, J. R., Roller, E., Eichelbaum, M., Klumpp, B., Krause, J., Schumacher, K., Hörner, S., Laßmann, A., Traugott, U., Schlick, E., Bürkle, D., Futscher BW, List AF, Dalton WS, Ladda, E., Bühl, K., Weimer, A., Eser, C., Hamprecht, K., Schalk, K. P., Jackisch, C., Brandt, B., Blum, M., Louwen, F., Schulz, K., Hanker, J. P., Rüther, U., Schmidt, A., Müller, H. A. G., Nunnensiek, C., Bader, H., Eisenberger, F., Jipp, P., Niethammer, B., Muller, C., Ling, V., Joncourt, F., Redmond, S., Stöhr, M., Buser, K., Fey, M., Tobler, A., Brunner, K., Gratwohl, A., Cerrry, T., Nuessler, V., Pelka-Fleischer, R., Nerl, C., Beckert, B., Wilmanns, W., Hegewisch-Becker, S., Fliegner, M., Zander, A., Hossfeld, D. K., Blanz, J., Mewes, K., Ehninger, G., Zeller, K. -P., Schuldes, H., Herrmann, G., Boeckmann, W., Schroeder, R., Jonas, D., Zurborn, K. -H., Bruhn, H. D., Uharek, L., Glass, B., Gassmann, W., Loeffler, H., Mueller-Ruohholtz, W., Gassmann W., Glass B., Uharek L., Loeffler H., Mueller-Ruchholtz W., Jaquet, K., Kreipe, H., Felgner, J., Radzun, H. J., Parwaresch, M. R., Kogan EA, Mazurenko NN, Sekamova SM, Wolf, H., Röhe, K., Wilkens, K., Clausen, M., Henze, E., van der Bosch, J., Rüller, S., Schlaak, M., Köhl, U., Schwabe, D., Rohrbach, E., Montag, E., Bauer, S., Cinatl, J., Cinatl, Jr, I., Mainke, M., Geiss, H., Kornhuber, B., Juhl, H., Stritzel, H., Kalhoff, H., Schniegel, W., Menke, T., Pröbsting, B., Schulze-Westhoff, P., Boos, J., Weidner, J., Wedemeyer, N., Wiedorn, K., Ueda, Y., Blasius, S., Wuisman, P., Böcker, W., Roessner, A., Dockhorn-Dworniczak, B., Ramm, D., Knebel, J., Sass, W., Aufderheide, M., and Seifert, J.

Published
1991
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7. Results of phase I clinical trial of high doses of seleno-l-methionine (SLM) in sequential combination with axitinib in previously treated and relapsed clear cell renal carcinoma (ccRCC) patients

Author

Zakharia, Y., primary, Garje, R., additional, Brown, J., additional, Nepple, K., additional, Bellizzi, A., additional, Bonner, J., additional, Parr, D., additional, Born, J., additional, Sieren, J., additional, Park, J., additional, Milhem, M., additional, and Rustum, Y., additional

Published
2019
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13. Design of Adjuvant Chemotherapy Based on Target Cell Determinants of Drug Action: Possibilities and Limitations

Author

Rustum, Y., Cheng, Y. C., Pavelic, Z., Creaven, P., Mihich, E., Allfrey, V. G., editor, Allgöwer, M., editor, Berenblum, I., editor, Bergel, F., editor, Bernard, J., editor, Bernhard, W., editor, Blokhin, N. N., editor, Bock, H. E., editor, Braun, W., editor, Bucalossi, P., editor, Chaklin, A. V., editor, Chorazy, M., editor, Cunningham, G. J., editor, Della Porta, G., editor, Denoix, P., editor, Dulbecco, R., editor, Eagle, H., editor, Eker, R., editor, Good, R. A., editor, Grabar, P., editor, Harris, R. J. C., editor, Hecker, E., editor, Herbeuval, R., editor, Higginson, J., editor, Hueper, W. C., editor, Isliker, H., editor, Kieler, J., editor, Kirsten, W. H., editor, Klein, G., editor, Koprowski, H., editor, Koss, L. G., editor, Martz, G., editor, Mathé, G., editor, Mühlbock, O., editor, Nakahara, W., editor, Old, L. J., editor, Potter, V. R., editor, Sabin, A. B., editor, Sachs, L., editor, Saxén, E. A., editor, Schmidt, C. G., editor, Spiegelman, S., editor, Szybalski, W., editor, Tagnon, H., editor, Taylor, R. M., editor, Tissières, A., editor, Uehlinger, E., editor, Wissler, R. W., editor, Rentchnick, P., editor, Bonadonna, Gianni, editor, Mathé, Georges, editor, and Salmon, Sydney E., editor

Published
1979
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25. MDR1 P-glycoprotein is expressed by endothelial cells of newly formed capillaries in human gliomas but is not expressed in the neovasculature of other primary tumors

Author

Tóth, K., Vaughan, M. M., Peress, N. S., Slocum, H. K., and Rustum, Y. M.

Subjects
Adult, endocrine system diseases, integumentary system, Neovascularization, Pathologic, Brain Neoplasms, Brain, Glioma, Immunohistochemistry, Drug Resistance, Multiple, Capillaries, polycyclic compounds, Humans, ATP Binding Cassette Transporter, Subfamily B, Member 1, Endothelium, Vascular, Research Article, Neoplasm Staging
Abstract

The expression of human MDR1 P-glycoprotein (Pgp) in the capillary endothelial cells of the central nervous system has been demonstrated. The brain capillary endothelial cells maintain the structure and function of the blood-brain barrier. Recently, the human MDR1 Pgp (and its mouse homologue MDR1a Pgp) has been shown to function as an important part of this barrier, pumping out xenobiotics from endothelial cells into the lumen of capillaries resulting in the protection of the brain parenchyma. To examine whether the endothelial cells of the newly formed capillaries during neoangiogenesis within malignant human brain tumors express MDR1 Pgp, 35 adult surgical brain tumor specimens (29 gliomas and 6 tumors metastatic to the brain) were obtained from previously untreated patients and studied by a new immunohistochemical sandwich method developed in our laboratory using the JSB-1 monoclonal antibody. JSB-1 is specific for the Pgp product of the human MDR1 (and not MDR3) gene. This sensitive method allows the detection of Pgp in capillary endothelial cells of normal brain in conventional paraffin sections after formalin fixation. The endothelial cells of the newly formed capillaries in 25 of 29 gliomas (86%) and 3 of 6 metastatic tumors, immunostained positive for MDR1 Pgp. The tumor cells in 7 of 35 cases were also positive for Pgp. In the 35 brain tumor cases investigated, the endothelial cells were Pgp positive in the tumor-brain border and in the brain further from the tumor. Capillary endothelial cells of neovasculature in 137 malignant tumors (non-brain) obtained from previously untreated patients showed no MDR1 Pgp expression. These results demonstrated that MDR1 Pgp is expressed not only in the capillaries of normal brain but also in the majority of the newly formed capillaries of brain tumors. Multidrug resistance of brain tumors may result not only from the expression of resistance markers in neoplastic cells but also from the MDR1 Pgp expression in endothelial cells of tumor capillaries. Pgp in this special localization can exclude chemotherapeutic agents from tumor cells that are located around the capillaries. The therapeutic benefit and selectivity of chemotherapeutic agents in combination with a Pgp-reversing agent should be evaluated.

Published
1996

27. Comparison of an immunoperoxidase 'sandwich' staining method and western blot detection of P-glycoprotein in human cell lines and sarcomas

Author

Tóth, K., Vaughan, M. M., Slocum, H. K., Fredericks, W. J., Chen, Y. F., Arredondo, M. A., Harstrick, A., Karakousis, C., Baker, R. M., and Rustum, Y. M.

Subjects
Immunoenzyme Techniques, Membrane Glycoproteins, Staining and Labeling, Evaluation Studies as Topic, Biopsy, Blotting, Western, polycyclic compounds, Humans, Sarcoma, ATP Binding Cassette Transporter, Subfamily B, Member 1, Carrier Proteins, Research Article, Cell Line
Abstract

The applicability of a multilayer immunoperoxidase "sandwich" method (IpS) developed by Chan14 for the amplified detection of P-glycoprotein (Pgp) was investigated. The authors examined 15 formalin-fixed cell lines, as well as formalin-fixed, paraffin-embedded sections from single biopsies of 46 sarcomas. The cell lines included sensitive and multidrug resistant sublines (KB, A2780, MCF-7, HeLa) with various relative degrees of resistance to doxorubicin (Dox). The sarcoma biopsy specimens were selected on the basis of the results obtained in Western blot (WB) detection of Pgp (22 positive and 24 negative by WB) using C219 and C494 monoclonal antibodies to Pgp. The IpS method employed C219. The least resistant cell line in which Pgp could be detected by IpS was fivefold resistant to doxorubicin, whereas Pgp was detected by WB in cells greater than twofold resistant. Cell lines having greater than fivefold resistance to Dox were positive by both IpS and WB analyses. The less resistant cell lines contained more nonreactive cells whereas the highly resistant cell lines showed more homogeneous strong membrane reactions. Among the six cell lines determined to be Pgp negative by WB analysis, no false positive immunostaining by IpS existed. One of 22 WB positive and 7 of 24 WB-negative sarcoma biopsy specimens were positive by IpS methods. Reaction varied and was always focal (a minimum of 3-5 cells, ranging up to 3-4 high power fields) indicating pronounced heterogeneous distribution of Pgp. Thus, WB can detect low average (overall) levels of Pgp in tumor samples but such low concentrations of PgP at the single cell are not detectable by IpS methods. However, IpS can discern among many Pgp-negative cells small subpopulations of immunoreactive cells, which are not detected by WB analysis due to Pgp dilution by the membrane protein of numerous Pgp negative cells. IpS and WB used together as complementary methods can provide more complete information about Pgp distribution and content, particularly in the case of heterogeneous human tumors. The IpS method is more suitable for less drastically treated (not embedded) cell line specimens than for paraffin-embedded (routine) sections. Some modification of the present IpS protocol seems necessary to increase its sensitivity and reduce the disparity with WB results.

Published
1992

41. Biological effects of recombinant human granulocyte colony-stimulating factor in patients with untreated acute myeloid leukemia

Author

Baer, MR, primary, Bernstein, SH, additional, Brunetto, VL, additional, Heinonen, K, additional, Mrozek, K, additional, Swann, VL, additional, Minderman, H, additional, Block, AW, additional, Pixley, LA, additional, Christiansen, NP, additional, Fay, JW, additional, Barcos, M, additional, Rustum, Y, additional, Herzig, GP, additional, and Bloomfield, CD, additional

Published
1996
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50. A phase I study of capecitabine and a modulatory dose of irinotecan in metastatic breast cancer.

Author

O'connor T, Rustum Y, Levine E, and Creaven P

Abstract

There is a need for chemotherapy regimens active against anthracycline- and taxane-refractory breast cancer. Data from preclinical and pilot studies performed at Roswell Park Cancer Institute (RPCI) suggested that when irinotecan (IRN) is given with 5-fluorouracil (5-FU) efficacy is affected by the sequence of drug administration. Pretreatment with IRN 24 h before 5-FU increased the number of tumor cells in S-phase and the antitumor activity in a preclinical system. These data provided the rationale for the evaluation of IRN and capecitabine, a 5-FU prodrug, sequentially administered in patients with metastatic breast cancer. The main objective of the study was to determine the MTD and identify dose-limiting toxicities (DLTs) of capecitabine and IRN. Additionally, the degree of accumulation of cells in S-phase in tumor biopsies obtained at 24 h after the first dose of IRN was measured in consenting patients. Metastatic breast cancer patients who experienced disease progression after at least one (taxane or anthracycline based) chemotherapy regimen and an expected survival of at least 3 months and ECOG performance status 0–2 were eligible. Twelve patients were enrolled and treated. The starting doses were IRN 80 mg/m2 given over 90 min on days 1, 8, 22, 29, and capecitabine 1,500 mg/m2/day given days 2–15 and 23–36. Evaluation for response was performed after the first cycle. Sequential tumor biopsies were performed on five patients. The first three patients treated exhibited modulation in cyclin A index on tumor biopsy as defined by the study, defining the modulatory dose of IRN as 80 mg/m2. Overall, 4/5 biopsies showed modulation. Dose Limiting Toxicities (DLTs) were assessed during the first cycle of therapy. Two DLTs (Grade 3 nausea vomiting and dehydration; grade 3 pneumonia, hypoxia, hypotension) were seen at dose level 2 of capecitabine (2,000 mg/m2/day) and the first cohort was expanded. There were no DLTs for patients treated at DL 1. No grade 3–4 toxicities occurred at DL 1. Seven patients were evaluable for response following one cycle of treatment (partial response 1, stable disease 4, progressive disease 2) Of the five inevaluable patients, two experienced DLT, one received 50% of the planned capecitabine dose, one progressed prior to evaluation, and one withdrew consent. IRN 80 mg/m2 days 1, 8, 22, 29 in combination with capecitabine 1,500 mg/m2/day in divided dose days 2–15 and 23–36 has an acceptable toxicity profile and resulted in modulation of S-phase in 4/5 specimens examined. Further studies of the activity of this combination and modulatory effect of IRN are warranted. [ABSTRACT FROM AUTHOR]

Published
2008

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