Antitumor activity of methotrexate‐albumin conjugates in rats bearing a Walker‐256 carcinoma

@article{Wunder1998AntitumorAO,
  title={Antitumor activity of methotrexate‐albumin conjugates in rats bearing a Walker‐256 carcinoma},
  author={Andreas Wunder and Gerd Stehle and Hans Hermann Schrenk and Gernot Hartung and Dieter L. Heene and W Maier-borst and Hannsjörg Sinn},
  journal={International Journal of Cancer},
  year={1998},
  volume={76}
}
We have recently reported that albumin accumulates in solid tumors and serves there as a source of nitrogen and energy. Methotrexate‐albumin conjugates [MTX(1)‐RSA] derivatized at a molar ratio of 1:1 differ favorably from original MTX in terms of plasma presence and tumor uptake. The purpose of this study was to evaluate the therapeutic efficacy of these novel conjugates in a comparative study with low m.w. MTX in Sprague‐Dawley rats bearing a Walker‐256 carcinoma. The maximum tolerated dose… Expand
Pre‐clinical evaluation of a methotrexate–albumin conjugate (MTX‐HSA) in human tumor xenografts in vivo
TLDR
The improved therapeutic effects seen in 3 xenograft models under MTX‐HSA treatment are promising and might be due to specific accumulation of the compound in solid tumors owing to their enhanced permeability and retention effect. Expand
Efficacy and tolerability of an aminopterin–albumin conjugate in tumor-bearing rats
TLDR
In this comparative study, the AMPT–SA conjugate showed high antitumor activity in vivo and a favorable toxicity compared to low-molecular-weight AMPT, which seems to be an effective tool for selective tumor drug targeting. Expand
Albumin-Based Drug Delivery as Novel Therapeutic Approach for Rheumatoid Arthritis1
We reported recently that albumin is a suitable drug carrier for targeted delivery of methotrexate (MTX) to tumors. Due to pathophysiological conditions in neoplastic tissue, high amounts of albuminExpand
Methotrexate-Albumin and Aminopterin-Albumin Effectively Prevent Experimental Acute Graft-versus-Host Disease
TLDR
The albumin conjugates MTX-HSA and aminopterin bound to HSA effectively prevent experimental aGVHD. Expand
Albumin-coupled methotrexate (MTX-HSA) is a new anti-arthritic drug which acts synergistically to MTX.
TLDR
The data show that the effectiveness of MTX-HSA in CIA is superior to MTX and that both drugs act synergistically, suggesting that they might be one of the potential target cells of this novel anti-arthritic treatment approach. Expand
Phase I trial of methotrexate-albumin in a weekly intravenous bolus regimen in cancer patients. Phase I Study Group of the Association for Medical Oncology of the German Cancer Society.
  • G. Hartung, G. Stehle, +10 authors W. Queisser
  • Medicine
  • Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1999
TLDR
This first Phase I study of MTX-HSA to determine dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) in a weekly regimen was well tolerated and tumor responses were seen, with no signs of toxicity or drug accumulation seen. Expand
Toxicity of a methotrexate metronomic schedule in Wistar rats.
TLDR
Evaluating the toxic effects of a metronomic oral dose of methotrexate (MTX) for 45 days in tumor-free Wistar rats when compared with control animals suggested that MTX metronome toxicity should not be neglected owing to the observed residual side-effects and special care should be taken regarding myelosuppression. Expand
A phase II trial of methotrexate-human serum albumin (MTX-HSA) in patients with metastatic renal cell carcinoma who progressed under immunotherapy
TLDR
MTX-HSA was generally well tolerated and can be given on an outpatient basis, but no objective responses were seen in patients with metastatic RCC who had progressed after previous immunotherapy. Expand
Methotrexate (MTX) and albumin coupled with MTX (MTX-HSA) suppress synovial fibroblast invasion and cartilage degradation in vivo.
TLDR
Treatment with MTX or MTX-HSA significantly ameliorates cartilage destruction in the SCID mouse model for human RA. Expand
A review of therapeutic challenges and achievements of methotrexate delivery systems for treatment of cancer and rheumatoid arthritis
TLDR
This review deals with the challenges of conventional systems and achievements of each pharmaceutical class of novel drug delivery vehicle and provides prolonged plasma profile, enhanced and specific activity in vitro and in vivo in animal models. Expand
...
1
2
3
4
...

References

SHOWING 1-10 OF 33 REFERENCES
Pharmacokinetics of methotrexate–albumin conjugates in tumor-bearing rats
TLDR
The potential therapeutic benefit of the MTX(1)-RSA conjugate lies in its very long tumor exposure time and its improved tumor accumulation rate compared to conventional MTX. Expand
Evolution of acute lymphoblastic leukemia in mice treated with carrier-bound methotrexate and levamisole.
TLDR
In vivo a single dose of 15 mg/kg MTX, which lacked therapeutic effect on tumor-bearing mice, increased the mean survival time (MST) of the animals when given as MTX-BSA. Expand
The loading rate determines tumor targeting properties of methotrexate albumin conjugates in rats
TLDR
It is shown that only loading rates of close to 1 mol of the cytostatic drug MTX/mol of albumin offer optimal conditions for targeting MTX-albumin conjugates into rodent tumors. Expand
The use of protein as a carrier of methotrexate for experimental cancer chemotherapy. IV. Therapy of murine melanoma B16 by human serum albumin-methotrexate derivative.
TLDR
It was found that the growth of tumor was slower after therapy with the HSA-MTX derivative than after free MTX treatment, and the reduction in tumor size recorded on day 21 after tumor transplantation was more significantly pronounced than in case of freeMTX treatment. Expand
Characterization of in‐vitro drug release and biological activity of methotrexate‐bovine serum albumin conjugates
TLDR
Two series of methotrexate (MTX)‐bovine serum albumin (BSA) conjugates have been prepared and retain a degree of antineoplastic activity in‐vitro, but this might be related to the small fraction of MTX that is tightly physically bound. Expand
The interaction of carrier-bound methotrexate with L1210 cells.
TLDR
MTX was as effective as free MTX and MTX bound to bovine serum albumin (MTX-BSA) in prolonging the life span of BDF1 mice bearing the L1210 tumor, suggesting that MTX can act as an effective chemotherapeutic agent when covalently bound to a variety of proteins. Expand
Differential toxicity of carrier-bound methotrexate toward human lymphocytes, marrow and tumor cells.
TLDR
The results suggest that comparable differential toxicity between marrow and tumor cells might also be achieved in vivo if MTX-PLL is infused over long periods at a rate that would maintain a constant serum concentration sufficient to kill tumor cells without affecting bone marrow cells. Expand
The organ targetability of small and large albumin microspheres containing free and HSA conjugated methotrexate
Abstract The organ-targeting ability of [ 3 H]methotrexate ([ 3 H]MTX), [ 3 H]MTX-human serum albumin (HSA) conjugates, and small (mean volume diameter, 10.0 μm) and large (mean volume diameter, 22.4Expand
Identification of tissue sites for increased albumin degradation in sarcoma-bearing mice.
TLDR
The tissue sites for increased albumin degradation in a nonmetastasizing sarcoma mouse model has been identified and there was a significantly decreased breakdown of albumin in both skeletal muscles and the gastrointestinal tract from tumor-bearing animals. Expand
Passive tumor targeting of soluble macromolecules and drug conjugates.
  • L. Seymour
  • Chemistry, Medicine
  • Critical reviews in therapeutic drug carrier systems
  • 1992
TLDR
The "enhanced permeability and retention effect" (EPR effect) has been studied extensively, and it is thought to constitute the mechanism of action of SMANCS (styrene-maleic/anhydride-neocarzinostatin), now in regular clinical use in Japan for the treatment of hepatoma. Expand
...
1
2
3
4
...