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Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Standard

Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. / Klement, Giannoula; Huang, Ping; Mayer, Barbara; Green, Shane K; Man, Shan; Bohlen, Peter; Hicklin, Daniel; Kerbel, Robert S.

I: Clinical Cancer Research, Bind 8, Nr. 1, 01.2002, s. 221-32.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Klement, G, Huang, P, Mayer, B, Green, SK, Man, S, Bohlen, P, Hicklin, D & Kerbel, RS 2002, 'Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts', Clinical Cancer Research, bind 8, nr. 1, s. 221-32.

APA

Klement, G., Huang, P., Mayer, B., Green, S. K., Man, S., Bohlen, P., ... Kerbel, R. S. (2002). Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. Clinical Cancer Research, 8(1), 221-32.

Vancouver

Klement G, Huang P, Mayer B, Green SK, Man S, Bohlen P o.a. Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. Clinical Cancer Research. 2002 jan;8(1):221-32.

Author

Klement, Giannoula ; Huang, Ping ; Mayer, Barbara ; Green, Shane K ; Man, Shan ; Bohlen, Peter ; Hicklin, Daniel ; Kerbel, Robert S. / Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. I: Clinical Cancer Research. 2002 ; Bind 8, Nr. 1. s. 221-32.

Bibtex

@article{c52e3fca45d747f4aa432a2d6ae8b60b,
title = "Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts",
abstract = "One of the greatest barriers to the treatment of cancer with chemotherapeutic drugs is acquisition of drug resistance. This includes multidrug resistance mediated by P-glycoprotein (Pgp) to multiple lipophilic natural compounds such as taxanes, doxorubicin (Adriamycin), and vinblastine. The considerable efforts made thus far to reverse this and other types of drug resistance have had very limited success. We report here that a variety of orthotopic human breast cancer xenografts selected for high levels of Pgp and multidrug resistance respond in a significant and durable manner to different continuous low-dose (e.g., one-tenth the maximum tolerated dose of chemotherapy) chemotherapy regimens, when used in combination with an antivascular endothelial cell growth factor (anti-VEGF) receptor-2 (flk-1)-neutralizing antibody (DC101). The Pgp substrates paclitaxel (Taxol), Adriamycin, and vinblastine were all effective using this type of combination treatment, although the chemotherapy protocols showed little or no effect as monotherapies. Similar results were also obtained using cisplatinum (a non-Pgp substrate drug) against cisplatinum-resistant tumors. Evidence of significant tumor cell death by the combination treatment was detected within 3 weeks of initiation of therapy by histopathological analysis, in the absence of shrinkage of tumor mass. There were, however, marked differences in the cumulative toxicity of long-term regimens of Adriamycin and cisplatinum, where toxicity was observed, when compared with the tubulin inhibitors, vinblastine and Taxol, where it was not. We conclude that vascular-targeting protocols involving frequent administration of very low doses of certain chemotherapeutic drugs can provide a stable and safe way to circumvent multidrug resistance in established orthotopically growing tumors, as long as these are used in combination with a second antiangiogenic drug, in this case, anti-VEGFR-2 blocking antibodies.",
keywords = "ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism, Animals, Antibodies, Monoclonal/therapeutic use, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Breast Neoplasms/drug therapy, Cisplatin/administration & dosage, Combined Modality Therapy, Cyclosporine/pharmacology, Doxorubicin/administration & dosage, Drug Resistance, Multiple, Drug Resistance, Neoplasm, Endothelium, Vascular/drug effects, Enzyme Inhibitors/pharmacology, Female, Humans, Mice, Mice, Nude, Paclitaxel/administration & dosage, Receptor Protein-Tyrosine Kinases/immunology, Receptors, Growth Factor/immunology, Receptors, Vascular Endothelial Growth Factor, Transplantation, Heterologous, Tubulin Modulators, Tumor Cells, Cultured, Vinblastine/administration & dosage",
author = "Giannoula Klement and Ping Huang and Barbara Mayer and Green, {Shane K} and Shan Man and Peter Bohlen and Daniel Hicklin and Kerbel, {Robert S}",
year = "2002",
month = "1",
language = "English",
volume = "8",
pages = "221--32",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research (A A C R)",
number = "1",

}

RIS

TY - JOUR

T1 - Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts

AU - Klement, Giannoula

AU - Huang, Ping

AU - Mayer, Barbara

AU - Green, Shane K

AU - Man, Shan

AU - Bohlen, Peter

AU - Hicklin, Daniel

AU - Kerbel, Robert S

PY - 2002/1

Y1 - 2002/1

N2 - One of the greatest barriers to the treatment of cancer with chemotherapeutic drugs is acquisition of drug resistance. This includes multidrug resistance mediated by P-glycoprotein (Pgp) to multiple lipophilic natural compounds such as taxanes, doxorubicin (Adriamycin), and vinblastine. The considerable efforts made thus far to reverse this and other types of drug resistance have had very limited success. We report here that a variety of orthotopic human breast cancer xenografts selected for high levels of Pgp and multidrug resistance respond in a significant and durable manner to different continuous low-dose (e.g., one-tenth the maximum tolerated dose of chemotherapy) chemotherapy regimens, when used in combination with an antivascular endothelial cell growth factor (anti-VEGF) receptor-2 (flk-1)-neutralizing antibody (DC101). The Pgp substrates paclitaxel (Taxol), Adriamycin, and vinblastine were all effective using this type of combination treatment, although the chemotherapy protocols showed little or no effect as monotherapies. Similar results were also obtained using cisplatinum (a non-Pgp substrate drug) against cisplatinum-resistant tumors. Evidence of significant tumor cell death by the combination treatment was detected within 3 weeks of initiation of therapy by histopathological analysis, in the absence of shrinkage of tumor mass. There were, however, marked differences in the cumulative toxicity of long-term regimens of Adriamycin and cisplatinum, where toxicity was observed, when compared with the tubulin inhibitors, vinblastine and Taxol, where it was not. We conclude that vascular-targeting protocols involving frequent administration of very low doses of certain chemotherapeutic drugs can provide a stable and safe way to circumvent multidrug resistance in established orthotopically growing tumors, as long as these are used in combination with a second antiangiogenic drug, in this case, anti-VEGFR-2 blocking antibodies.

AB - One of the greatest barriers to the treatment of cancer with chemotherapeutic drugs is acquisition of drug resistance. This includes multidrug resistance mediated by P-glycoprotein (Pgp) to multiple lipophilic natural compounds such as taxanes, doxorubicin (Adriamycin), and vinblastine. The considerable efforts made thus far to reverse this and other types of drug resistance have had very limited success. We report here that a variety of orthotopic human breast cancer xenografts selected for high levels of Pgp and multidrug resistance respond in a significant and durable manner to different continuous low-dose (e.g., one-tenth the maximum tolerated dose of chemotherapy) chemotherapy regimens, when used in combination with an antivascular endothelial cell growth factor (anti-VEGF) receptor-2 (flk-1)-neutralizing antibody (DC101). The Pgp substrates paclitaxel (Taxol), Adriamycin, and vinblastine were all effective using this type of combination treatment, although the chemotherapy protocols showed little or no effect as monotherapies. Similar results were also obtained using cisplatinum (a non-Pgp substrate drug) against cisplatinum-resistant tumors. Evidence of significant tumor cell death by the combination treatment was detected within 3 weeks of initiation of therapy by histopathological analysis, in the absence of shrinkage of tumor mass. There were, however, marked differences in the cumulative toxicity of long-term regimens of Adriamycin and cisplatinum, where toxicity was observed, when compared with the tubulin inhibitors, vinblastine and Taxol, where it was not. We conclude that vascular-targeting protocols involving frequent administration of very low doses of certain chemotherapeutic drugs can provide a stable and safe way to circumvent multidrug resistance in established orthotopically growing tumors, as long as these are used in combination with a second antiangiogenic drug, in this case, anti-VEGFR-2 blocking antibodies.

KW - ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism

KW - Animals

KW - Antibodies, Monoclonal/therapeutic use

KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use

KW - Breast Neoplasms/drug therapy

KW - Cisplatin/administration & dosage

KW - Combined Modality Therapy

KW - Cyclosporine/pharmacology

KW - Doxorubicin/administration & dosage

KW - Drug Resistance, Multiple

KW - Drug Resistance, Neoplasm

KW - Endothelium, Vascular/drug effects

KW - Enzyme Inhibitors/pharmacology

KW - Female

KW - Humans

KW - Mice

KW - Mice, Nude

KW - Paclitaxel/administration & dosage

KW - Receptor Protein-Tyrosine Kinases/immunology

KW - Receptors, Growth Factor/immunology

KW - Receptors, Vascular Endothelial Growth Factor

KW - Transplantation, Heterologous

KW - Tubulin Modulators

KW - Tumor Cells, Cultured

KW - Vinblastine/administration & dosage

M3 - Journal article

C2 - 11801563

VL - 8

SP - 221

EP - 232

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 1

ER -

ID: 218726724